Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running o...Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.展开更多
Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic dise...Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.展开更多
BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are ...BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.展开更多
Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebr...Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebra Finch(Taeniopygia guttata),we investigated the effects of short-term night lighting on liver transcriptome,blood glucose,triglyceride,and thyroxine(T4 and T3)levels in birds exposed to two different night lighting duration periods(three days and six days).After three days of night lighting exposure,the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated.There was also a reduction in blood triglyceride,glucose,and T3 concentrations.However,after six days of night lighting,the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated,while the expression of genes involved in fat synthesis was downregulated.Simultaneously,blood glucose levels and T3 concentration increased.These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds,and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.展开更多
BACKGROUND Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment,with adver...BACKGROUND Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment,with adverse effects on glucose metabolism.Disorders associated with glucose metabolism are established risk factors of cardiovascular events,one of the life-threatening ramifications.AIM To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone(Pred)replacement,and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes.METHODS Twenty patients with hypopituitarism receiving Pred replacement[patient group(PG)]and 20 normal controls(NCs)were recruited.A flash glucose monitoring system was used to record continuous glucose levels during the day,which provided information on glucose-target-rate,glucose variability(GV),period glucose level,and hypoglycemia occurrence at certain periods.Islet β-cell function was also assessed.Based on the administered Pred dose per day,the PG was then regrouped into Pred>5 mg/d and Pred≤5 mg/d subgroups.Comparative analysis was carried out between the PG and NCs.RESULTS Significantly altered glucose metabolism profiles were identified in the PG.This includes significant reductions in glucose-target-rate and nocturnal glucose level,along with elevations in GV,hypoglycemia occurrence and postprandial glucose level,when compared with those in NCs.Subgroup analysis indicated more significant glucose metabolism impairment in the Pred>5 mg/d group,including significantly decreased glucose-target-rate and nocturnal glucose level,along with increased GV,hypoglycemia occurrence,and postprandial glucose level.With regard to islet β-cell function,PG showed significant difference in homeostasis model assessment(HOMA)-β compared with that of NCs;a notable difference in HOMA-βwas identified in Pred>5 mg/d group when compared with those of NCs;as for Pred≤5 mg/d group,significant differences were found in HOMA-β,and fasting glucose/insulin ratio when compared with NCs.CONCLUSION Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism.A Pred dose of>5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of≤5 mg/d.Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen,wherein,flash glucose monitoring system is a kind of promising and reliable assessment device.The present data allows us to thoroughly examine our modern treatment standards,especially in difficult cases such as hormonal replacement mimicking delicate natural cycles,in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.展开更多
Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,...Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,these localized forms of steroid therapy are generally considered to have fewer systemic side effects compared to long-term oral corticosteroids.However,concern and controversy remain over the impact of ICS and INS on the incidence and control of diabetes mellitus(DM).Given the widespread use of ICS and INS,even small individual effects on DM could lead to large consequences for the global population.Multiple large observational studies suggest that high dose ICS is associated with increased incident DM and worsened DM control,though the contribution of other risk factors is less certain.In addition,only two studies were done to investigate the association of INS and DM,with both studies demonstrating a short-term association of INS use with hyperglycemia.While more research evaluating the risk of ICS/INS for DM-related adverse events is needed,high doses of ICS/INS should be avoided when possible.The following strategies for ICS/INS dose minimization can be considered:Use of non-pharmacological measures(trigger avoidance,smoking cessation,vaccination to avoid infection),control of comorbid conditions,use of non-ICS-containing medications,intermittent rather than regular ICS dosing,and appropriate de-escalation of high ICS doses.展开更多
BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plu...BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.展开更多
Background:Previous studies have shown that exogenous short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of e...Background:Previous studies have shown that exogenous short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota.This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free(GF)pig model.Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators.All pigs were hand-fed with sterile milk powder for 21 d,then the sterile feed was introduced to pigs for another 21 d.In the second 21-d period,six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group,while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture(acetic,propionic,and butyric acids,45,15,and 11 mmol/L,respectively)per day and regarded as FA group.Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum,enhance the CPT-1 activity in longissimus dorsi,and upregulate the ANGPTL4 mRNA expression level in colon(P<0.10).Meanwhile,the mRNA abundances of ACC,FAS,and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased(P<0.05)compared with those in the GF group.Besides,the mRNA expression of PGC-1αin liver and LPL in longissimus dorsi tended to(P<0.10)upregulate and downregulate respectively in the FA group.Moreover,oral administration of SCFAs tended to increase the protein level of GPR43(P<0.10)and decrease the protein level of ACC(P<0.10)in liver.Also,oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver(P<0.05).In addition,the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted(P<0.05)by oral administration of SCFAs.Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model,which occurred independently of the gut microbiota.展开更多
Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats...Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin(HFD/STZ)-induced diabetes.Specifically,we fully assessed the blood biochemical profiles,pancreatic histopathology,insulin-glucagon immunofluorescence,short-chain fatty acids,and gut microbiota composition of rats with HFD/STZ-induced diabetes before and after FM supplementation.Results showed that both 30% and 48% FM supplementation significantly decreased concentrations of fasting blood glucose,60-min blood glucose,and blood triglycerides(P<0.05);additionally,48% FM supplementation significantly improved blood glucose tolerance and insulin resistance(P<0.05).However,FM supplementation could not effectively repair damage to β-cells over a short period of time.In addition,4 weeks of 48% FM supplementation siginificantly increased the relative abundance of Bifidobacterium and concentration of butyrate,suggesting that the hypoglycemic effects of FM supplementation might be partially mediated by gut microbiota.Collectively,we found a dose-dependent relationship between FM supplementation and improvement of blood glucose metabolism,but did not find a synergistic effect between FM supplementation and metformin(Met)treatment.Our findings provide further support that consuming more whole-grain FM might be beneficial to individuals suffering from type 2 diabetes.展开更多
BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered asso...BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.展开更多
Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus....Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.展开更多
To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hyp...To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.展开更多
Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with ge...Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.展开更多
Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resist...Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.展开更多
AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transport...AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transporter 1(GLUT1),and whole-body ^(18)F-FDG PET/c T for measuring tumour glucose uptake were performed in 55 newly diagnosed Hcc patients.The maximum standard uptake value(s UVmax)and tumour-to-non-tumourous liver uptake(T/NT)ratio were used to quantify ^(18)F-FDG uptake.In vitro ^(18)F-FDG uptake assay of GPc3-expressing Hep G2 and non-GPc3-expressing RH7777 cel ls was used to examine the effect of GPc3 in cellular glucose metabolism.The relationships between GPc3 expression and ^(18)F-FDG uptake,GLUT1 expression,tumour differentiation,and other clinical indicators were analysed using spearman rank correlation,univariateand multiple logistic regression analyses.RESULTSPositive GPc3 expression was observed in 67.3%of Hcc patients,including 75.0%of those with well or moderately differentiated Hcc and 36.4%of those with poorly differentiated Hcc.There was an inverse relationship between GPc3 expression and s UVmax(Spearman correlation coefficient=-0.281,P=0.038)and a positive relationship between GLUT1 expression and sU Vmax(Spearman correlation coefficient=0.681,P<0.001)in patients with Hcc.Univariate analysis showed that two glucose metabolic parameters(sU Vmax and T/NT ratio),tumour differentiation,lymph node metastasis,and TNM stage were all significantly associated with GPc3 expression(P<0.05),whereas GLUT1 expression,sex,age,tumour size,intrahepatic lesion number,and distant metastasis showed no statistical association(P>0.05).Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with Hcc(P<0.05).In vitro assay revealed that the uptake of ^(18)F-FDG in GPc3-expressing HepG2 cells was significantly lower than that of non-GPc3-expressing RH7777 cells(t=-20.352,P<0.001).CONCLUSIONThe present study demonstrated that GPc3 expression is inversely associated with glucose metabolism,suggesting that GPc3 may play a role in regulating glucose metabolism in Hcc.展开更多
OBJECTIVE To investigate the protective effect of icariin(ICA) on learning and memory function in APP/PS1/Tau triple transgenic Alzheimer disease mice(3×Tg-AD mice),and then to explore whether its mechanism is re...OBJECTIVE To investigate the protective effect of icariin(ICA) on learning and memory function in APP/PS1/Tau triple transgenic Alzheimer disease mice(3×Tg-AD mice),and then to explore whether its mechanism is related to the improvement of brain glucose metabolism disorder.METHODS Three-month-old male 3 ×Tg-AD mice were randomly divided into three groups(n=10):3×Tg group,3×Tg+ICA low-dose group(30 mg·kg-1) and 3×Tg + ICA high-dose group(60 mg·kg-1).Age-matched male wild type(WT) mice were randomly divided into two groups(n=10):WT control group and WT+ICA60 mg·kg-1 group.ICA in vehicle(0.5% Tween-80 in distilled water) was given orally once a day for five months in the 3×Tg+ICA groups.3×Tg and WT control group were given an equal volume vehicle.Morris water maze was used to detect the learning and memory function of mice.Brain glucose metabolism in 3×Tg mice was observed by 18 F-FDG microPET imaging technique.Nissl staining and HE staining were used to evaluate the survival neurons in hippocampus of mice.Glucose oxidase assay was used to detect glucose contents in cortex of mice.The protein expression of APP,Aβ1-40,Aβ1-42 and glucose transporter 1(GLUT1),and the phosphorylation level of tau protein at multiple sites in hippocampus were detected by Western blotting.RESULTS Behavioral examination revealed a profound decrease learning and memory function,accompanied by a decrease in number of neuronal cells in 3×Tg-AD mice.Moreover,the cerebral18 F-FDG uptake rate per gram tissue was reduced and the glucose contents in the cortex were increased in 3×Tg-AD mice.In addition,Western blotting analysis showed that the expression of APP,Aβ1-40,Aβ1-42 proteins and the levels of tau protein phosphorylation at Ser199/202 and PHF-1(Ser396/404) sites were increased significantly,followed by a decrease of GLUT1 expression in hippocampus of 3×Tg-AD mice.All of these changes in behavioral functions,neuronal loss and related protein expression were reversed when mice were treated with ICA.CONCLUSION ICA can improve the learning and memory ability of AD model mice,the mechanism may be related to the improvement of cerebral glucose metabolism dysfunction by increasing the expression of GLUT1.展开更多
The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specificall...The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.展开更多
OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS...OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.展开更多
Objective:To explore the protective effect of the drug Semecarpus anacardium(S.anacardium) on altered glucose metabolism in diabetic rats.Methods:Type 2 diabetes mellitus was induced by feeding rats with high fat diet...Objective:To explore the protective effect of the drug Semecarpus anacardium(S.anacardium) on altered glucose metabolism in diabetic rats.Methods:Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ)(35 mg/kg b.w.).Seven days after STZ induction,diabetic rats received nut milk extract of S.anacardium Linn.nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks.The effect of nut milk extract of S.anacardium on blood glucose,plasma insulin,glucose metabolising enzymes and GSK were studied.Results:Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA-βand decrease in HOMA -IR.The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes.The drug also effectively ameliorated the alterations in GSK-3 mRNA expression.Conclusions:Overall,the present study demonstrates the possible mechanism of glucose regulation of S.anacardium suggestive of its therapeutic potential for the management of diabetes mellitus.展开更多
Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due t...Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.展开更多
基金sponsored by National Natural Science Foundation of China (81800703 and 81970701)Beijing Nova Program (Z201100006820117 and 20220484181)+7 种基金Beijing Municipal Natural Science Foundation (7184252 and 7214258)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities (BMU2021MX013)Peking University Clinical Scientist Training Program (BMU2023PYJH022)China Endocrine and Metabolism Young Scientific Talent Research Project (2022-N-02-01)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation (G2018030)。
文摘Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.
基金supported by Karolinska Institutet in the form of a Board of Research Faculty Funded Career Positionby St.Erik Eye Hospital philanthropic donations+1 种基金Vetenskapsr?det2022-00799(to PAW)Alcon Research Institute Young Investigator。
文摘Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.
基金the National Natural Science Foundation of China, No. 81600617
文摘BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.
基金supported by grants from Key laboratory of Ecology and Environment in Minority Area,National Ethnic Affairs Commission(KLEEMA202207)the Graduate Research and Practice Projects of Minzu University of China(BZKY2022042).
文摘Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebra Finch(Taeniopygia guttata),we investigated the effects of short-term night lighting on liver transcriptome,blood glucose,triglyceride,and thyroxine(T4 and T3)levels in birds exposed to two different night lighting duration periods(three days and six days).After three days of night lighting exposure,the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated.There was also a reduction in blood triglyceride,glucose,and T3 concentrations.However,after six days of night lighting,the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated,while the expression of genes involved in fat synthesis was downregulated.Simultaneously,blood glucose levels and T3 concentration increased.These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds,and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.
基金Supported by National Natural Science Foundation of China,No.81770776,No.81973378,and No.82073909The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059Postgraduate Education Innovation Project of Shanxi Province,No.2022Y354.
文摘BACKGROUND Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment,with adverse effects on glucose metabolism.Disorders associated with glucose metabolism are established risk factors of cardiovascular events,one of the life-threatening ramifications.AIM To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone(Pred)replacement,and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes.METHODS Twenty patients with hypopituitarism receiving Pred replacement[patient group(PG)]and 20 normal controls(NCs)were recruited.A flash glucose monitoring system was used to record continuous glucose levels during the day,which provided information on glucose-target-rate,glucose variability(GV),period glucose level,and hypoglycemia occurrence at certain periods.Islet β-cell function was also assessed.Based on the administered Pred dose per day,the PG was then regrouped into Pred>5 mg/d and Pred≤5 mg/d subgroups.Comparative analysis was carried out between the PG and NCs.RESULTS Significantly altered glucose metabolism profiles were identified in the PG.This includes significant reductions in glucose-target-rate and nocturnal glucose level,along with elevations in GV,hypoglycemia occurrence and postprandial glucose level,when compared with those in NCs.Subgroup analysis indicated more significant glucose metabolism impairment in the Pred>5 mg/d group,including significantly decreased glucose-target-rate and nocturnal glucose level,along with increased GV,hypoglycemia occurrence,and postprandial glucose level.With regard to islet β-cell function,PG showed significant difference in homeostasis model assessment(HOMA)-β compared with that of NCs;a notable difference in HOMA-βwas identified in Pred>5 mg/d group when compared with those of NCs;as for Pred≤5 mg/d group,significant differences were found in HOMA-β,and fasting glucose/insulin ratio when compared with NCs.CONCLUSION Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism.A Pred dose of>5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of≤5 mg/d.Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen,wherein,flash glucose monitoring system is a kind of promising and reliable assessment device.The present data allows us to thoroughly examine our modern treatment standards,especially in difficult cases such as hormonal replacement mimicking delicate natural cycles,in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.
文摘Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,these localized forms of steroid therapy are generally considered to have fewer systemic side effects compared to long-term oral corticosteroids.However,concern and controversy remain over the impact of ICS and INS on the incidence and control of diabetes mellitus(DM).Given the widespread use of ICS and INS,even small individual effects on DM could lead to large consequences for the global population.Multiple large observational studies suggest that high dose ICS is associated with increased incident DM and worsened DM control,though the contribution of other risk factors is less certain.In addition,only two studies were done to investigate the association of INS and DM,with both studies demonstrating a short-term association of INS use with hyperglycemia.While more research evaluating the risk of ICS/INS for DM-related adverse events is needed,high doses of ICS/INS should be avoided when possible.The following strategies for ICS/INS dose minimization can be considered:Use of non-pharmacological measures(trigger avoidance,smoking cessation,vaccination to avoid infection),control of comorbid conditions,use of non-ICS-containing medications,intermittent rather than regular ICS dosing,and appropriate de-escalation of high ICS doses.
基金Supported by The Twelfth Five-Year Project on Tackling Key Problems of National Science and Technology,No2012ZX10001-003Sichuan Province Health Commission,No. 130430 and No. 17PJ070Chengdu Municipal Health Commission,No. 2019079
文摘BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.
基金study was supported by National Natural Science Foundation of China(31730091)the National Key Research and Development Program of China(2017YFD0500503).
文摘Background:Previous studies have shown that exogenous short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota.This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free(GF)pig model.Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators.All pigs were hand-fed with sterile milk powder for 21 d,then the sterile feed was introduced to pigs for another 21 d.In the second 21-d period,six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group,while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture(acetic,propionic,and butyric acids,45,15,and 11 mmol/L,respectively)per day and regarded as FA group.Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum,enhance the CPT-1 activity in longissimus dorsi,and upregulate the ANGPTL4 mRNA expression level in colon(P<0.10).Meanwhile,the mRNA abundances of ACC,FAS,and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased(P<0.05)compared with those in the GF group.Besides,the mRNA expression of PGC-1αin liver and LPL in longissimus dorsi tended to(P<0.10)upregulate and downregulate respectively in the FA group.Moreover,oral administration of SCFAs tended to increase the protein level of GPR43(P<0.10)and decrease the protein level of ACC(P<0.10)in liver.Also,oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver(P<0.05).In addition,the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted(P<0.05)by oral administration of SCFAs.Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model,which occurred independently of the gut microbiota.
基金supported by the National Key R&D Program of China(2017YFD0401200)China Agriculture Research System(CARS-07-13.5-A17)+1 种基金General S&T project of Beijing Municipal Commission of Education(KM202010011006)BTBU Youth Fund(PXM2019_014213_000007).
文摘Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin(HFD/STZ)-induced diabetes.Specifically,we fully assessed the blood biochemical profiles,pancreatic histopathology,insulin-glucagon immunofluorescence,short-chain fatty acids,and gut microbiota composition of rats with HFD/STZ-induced diabetes before and after FM supplementation.Results showed that both 30% and 48% FM supplementation significantly decreased concentrations of fasting blood glucose,60-min blood glucose,and blood triglycerides(P<0.05);additionally,48% FM supplementation significantly improved blood glucose tolerance and insulin resistance(P<0.05).However,FM supplementation could not effectively repair damage to β-cells over a short period of time.In addition,4 weeks of 48% FM supplementation siginificantly increased the relative abundance of Bifidobacterium and concentration of butyrate,suggesting that the hypoglycemic effects of FM supplementation might be partially mediated by gut microbiota.Collectively,we found a dose-dependent relationship between FM supplementation and improvement of blood glucose metabolism,but did not find a synergistic effect between FM supplementation and metformin(Met)treatment.Our findings provide further support that consuming more whole-grain FM might be beneficial to individuals suffering from type 2 diabetes.
基金Supported by the National Natural Science Foundation of China,No.82070455Natural Science Foundation of Jiangsu Province,No.BK20201225+1 种基金Medical Innovation Team Project of Jiangsu Province,No.CXTDA2017010Research and Innovation Funding Project for College Students in Experimental Animal Center of Jiangsu University。
文摘BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.
基金supported by National Natural Science Foundation of China(31900292)Science and Technology Development Program of Henan Province(202102110149,192102110112,and 182102410083)Science and Technology Project of Kaifeng(1908005,and 1803010).
文摘Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.
文摘To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.
基金Supported by The China Scholarship CouncilNo.[2014]3012
文摘Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.
文摘Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.
基金supported by the National Natural Science Foundation of China,No.81371591
文摘AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transporter 1(GLUT1),and whole-body ^(18)F-FDG PET/c T for measuring tumour glucose uptake were performed in 55 newly diagnosed Hcc patients.The maximum standard uptake value(s UVmax)and tumour-to-non-tumourous liver uptake(T/NT)ratio were used to quantify ^(18)F-FDG uptake.In vitro ^(18)F-FDG uptake assay of GPc3-expressing Hep G2 and non-GPc3-expressing RH7777 cel ls was used to examine the effect of GPc3 in cellular glucose metabolism.The relationships between GPc3 expression and ^(18)F-FDG uptake,GLUT1 expression,tumour differentiation,and other clinical indicators were analysed using spearman rank correlation,univariateand multiple logistic regression analyses.RESULTSPositive GPc3 expression was observed in 67.3%of Hcc patients,including 75.0%of those with well or moderately differentiated Hcc and 36.4%of those with poorly differentiated Hcc.There was an inverse relationship between GPc3 expression and s UVmax(Spearman correlation coefficient=-0.281,P=0.038)and a positive relationship between GLUT1 expression and sU Vmax(Spearman correlation coefficient=0.681,P<0.001)in patients with Hcc.Univariate analysis showed that two glucose metabolic parameters(sU Vmax and T/NT ratio),tumour differentiation,lymph node metastasis,and TNM stage were all significantly associated with GPc3 expression(P<0.05),whereas GLUT1 expression,sex,age,tumour size,intrahepatic lesion number,and distant metastasis showed no statistical association(P>0.05).Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with Hcc(P<0.05).In vitro assay revealed that the uptake of ^(18)F-FDG in GPc3-expressing HepG2 cells was significantly lower than that of non-GPc3-expressing RH7777 cells(t=-20.352,P<0.001).CONCLUSIONThe present study demonstrated that GPc3 expression is inversely associated with glucose metabolism,suggesting that GPc3 may play a role in regulating glucose metabolism in Hcc.
基金National Natural Science Foundation of China(81660599)Foundation of Zunyi Medical University (2013F-686+1 种基金2013F-738)Postgraduate Education Foundation of Guizhou Province(KYJJ2017008).
文摘OBJECTIVE To investigate the protective effect of icariin(ICA) on learning and memory function in APP/PS1/Tau triple transgenic Alzheimer disease mice(3×Tg-AD mice),and then to explore whether its mechanism is related to the improvement of brain glucose metabolism disorder.METHODS Three-month-old male 3 ×Tg-AD mice were randomly divided into three groups(n=10):3×Tg group,3×Tg+ICA low-dose group(30 mg·kg-1) and 3×Tg + ICA high-dose group(60 mg·kg-1).Age-matched male wild type(WT) mice were randomly divided into two groups(n=10):WT control group and WT+ICA60 mg·kg-1 group.ICA in vehicle(0.5% Tween-80 in distilled water) was given orally once a day for five months in the 3×Tg+ICA groups.3×Tg and WT control group were given an equal volume vehicle.Morris water maze was used to detect the learning and memory function of mice.Brain glucose metabolism in 3×Tg mice was observed by 18 F-FDG microPET imaging technique.Nissl staining and HE staining were used to evaluate the survival neurons in hippocampus of mice.Glucose oxidase assay was used to detect glucose contents in cortex of mice.The protein expression of APP,Aβ1-40,Aβ1-42 and glucose transporter 1(GLUT1),and the phosphorylation level of tau protein at multiple sites in hippocampus were detected by Western blotting.RESULTS Behavioral examination revealed a profound decrease learning and memory function,accompanied by a decrease in number of neuronal cells in 3×Tg-AD mice.Moreover,the cerebral18 F-FDG uptake rate per gram tissue was reduced and the glucose contents in the cortex were increased in 3×Tg-AD mice.In addition,Western blotting analysis showed that the expression of APP,Aβ1-40,Aβ1-42 proteins and the levels of tau protein phosphorylation at Ser199/202 and PHF-1(Ser396/404) sites were increased significantly,followed by a decrease of GLUT1 expression in hippocampus of 3×Tg-AD mice.All of these changes in behavioral functions,neuronal loss and related protein expression were reversed when mice were treated with ICA.CONCLUSION ICA can improve the learning and memory ability of AD model mice,the mechanism may be related to the improvement of cerebral glucose metabolism dysfunction by increasing the expression of GLUT1.
文摘The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.
基金National Natural Science Foundation of China(81530100,81673802,81673712,81822049)。
文摘OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.
基金financial assistance offered in the form of UGC RFSMS
文摘Objective:To explore the protective effect of the drug Semecarpus anacardium(S.anacardium) on altered glucose metabolism in diabetic rats.Methods:Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ)(35 mg/kg b.w.).Seven days after STZ induction,diabetic rats received nut milk extract of S.anacardium Linn.nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks.The effect of nut milk extract of S.anacardium on blood glucose,plasma insulin,glucose metabolising enzymes and GSK were studied.Results:Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA-βand decrease in HOMA -IR.The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes.The drug also effectively ameliorated the alterations in GSK-3 mRNA expression.Conclusions:Overall,the present study demonstrates the possible mechanism of glucose regulation of S.anacardium suggestive of its therapeutic potential for the management of diabetes mellitus.
文摘Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.
