Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the pho...Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.展开更多
With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic ...With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.展开更多
The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in Wor...The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.展开更多
BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is ...BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.展开更多
Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence...Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence of insulin resistance and associated risk factors in diabetic patients in the Democratic Republic of Congo between 2005 and 2023. Method: We measured fasting blood glucose and insulin levels and looked for metabolic syndrome parameters (2009 criteria) in type 2 diabetes patients in 2005-2008 (n = 176) and in 2018-2023 (n = 303). The HOMA model was used to measure insulin sensitivity and islet β-cell secretory function. Results: Between 2005 and 2013, the trend was towards an increase in the prevalence of insulin resistance (from 13.1% to 50.8%;p Conclusion: This present study shows an increase in insulin resistance in Congolese urban areas and a persistence of atypical diabetes mellitus in Congolese rural areas, confirming the particularity of the pathophysiology of the disease in African areas currently influenced by the epidemiological transition. Further studies using an appropriate methodology are required.展开更多
Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood...Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood,selenoprotein P,seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms.Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion.This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.展开更多
The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiologic...The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.展开更多
BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically studied.There is a lack of kn...BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically studied.There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents,despite their continuous rise.AIM To investigate the association between CRF and insulin resistance in obese adolescents,with special emphasis on severely obese adolescents.METHODS We performed a prospective,cross-sectional study that included 200 pubertal adolescents,10 years to 18 years of age,who were referred to a tertiary care center due to obesity.According to body mass index(BMI),adolescents were classified as mildly obese(BMI 100% to 120% of the 95^(th)percentile for age and sex)or severely obese(BMI≥120% of the 95^(th)percentile for age and sex or≥35 kg/m^(2),whichever was lower).Participant body composition was assessed by bioelectrical impedance analysis.A homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.Maximal oxygen uptake(VO_(2)max)was determined from submaximal treadmill exercise test.CRF was expressed as VO_(2)max scaled by total body weight(TBW)(mL/min/kg TBW)or by fat free mass(FFM)(mL/min/kg FFM),and then categorized as poor,intermediate,or good,according to VO_(2)max terciles.Data were analyzed by statistical software package SPSS(IBM SPSS Statistics for Windows,Version 24.0).P<0.05 was considered statistically significant.RESULTS A weak negative correlation between CRF and HOMA-IR was found[Spearman’s rank correlation coefficient(rs)=-0.28,P<0.01 for CRF_(TBW);(r_(s))=-0.21,P<0.01 for CRF_(FFM)].One-way analysis of variance(ANOVA)revealed a significant main effect of CRF on HOMA-IR[F(2200)=6.840,P=0.001 for CRF_(TBW);F_((2200))=3.883,P=0.022 for CRF_(FFM)].Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF(P=0.001 for CRF_(TBW);P=0.018 for CRF_(FFM)).Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR[F_((2200))=3.292,P=0.039 for CRF_(TBW)].Severely obese adolescents had higher HOMA-IR than those who were mildly obese,with either good or poor CRF.However,HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF.CONCLUSION CRF is an important determinant of insulin resistance in obese adolescents,regardless of obesity category.Therefore,CRF assessment should be a part of diagnostic procedure,and its improvement should be a therapeutic goal.展开更多
Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how centra...Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedent...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the rela...BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.展开更多
Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology me...Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.展开更多
Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on...Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on chemical constituents and hypoglycemic activity of P.scabiosaefolia,4 lignan compounds,(+)-isolariciresinol(1),7R,7’R,8S,8’S-(+)-neo-olivil-4-O-β-D-glucopyranoside(2),4-O-methylcedrusin(3)and patrinian A(4),were isolated and identifi ed.The hypoglycemic activity showed that compounds 2 and 3 could extremely signifi cantly improve insulin resistance at 100(P<0.001),50(P<0.001)and 25μmol/L(P<0.01)in IR 3T3-L1 cells.While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100μmol/L(P<0.01).Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS,PI-3K,p-AKT and glucose transporter 4(GLUT4),and promoted the transcription of GLUT4 mRNA.Therefore,the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.展开更多
Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in th...Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.展开更多
This paper discusses the mechanism of insulin resistance in obesity from the research progress of Chinese and Western medicine and its oxidative stress,inflammatory reaction and abnormal lipid metabolism in cognitive ...This paper discusses the mechanism of insulin resistance in obesity from the research progress of Chinese and Western medicine and its oxidative stress,inflammatory reaction and abnormal lipid metabolism in cognitive dysfunction.It also reviews the research progress of massage,one of the external treatment methods of traditional Chinese medicine,in the treatment of insulin resistance and cognitive dysfunction in obesity,in order to provide more new ideas and new ways for clinical diagnosis and treatment of insulin resistance and related cognitive dysfunction caused by obesity.展开更多
Objective:To investigate the clinical efficacy and effects on sex hormone level and glucose metabolism indexes of acupuncture therapy combined with the Bushen Huatan Huoxue Recipe in patients with polycystic ovary syn...Objective:To investigate the clinical efficacy and effects on sex hormone level and glucose metabolism indexes of acupuncture therapy combined with the Bushen Huatan Huoxue Recipe in patients with polycystic ovary syndrome(PCOS)with insulin resistance(IR).Methods:The patients with PCOS-IR admitted from December 2021 to December 2022 were randomly divided into two groups,30 cases in each group.The comparison one and the observation one were given the relevant treatment of metformin and traditional Chinese medicine combined with acupuncture,respectively.The evidence points,sex hormone indexes and glucose metabolism indexes were compared between the two groups before and after treatment,and the insulin resistance index(HOMA-IR),glucose area under the curve(GLU-AUC)and blood insulin area under the curve(INS-AUC)were calculated.Results:The evidence points of the observation group of patients were less than the pre-treatment and comparison groups;after treatment,the follicle-stimulating hormone(FSH)level of patients in the observation group was more than the control and pre-treatment groups(P<0.05),and the ratio of luteinizing hormone(LH)to follicle-stimulating hormone(FSH)was less than that of the comparison and pre-treatment groups(P<0.05),and the levels of LH and testosterone(T)were reduced to varying degrees in both groups around the time of treatment(P<0.05).The patients in the observation group had lower levels of 0.5hPG than those in the comparison group and pretreatment(both P<0.05),and the levels of 3hPG in both groups were lower than those before treatment(P<0.05).The oral OGIRT in each of the two groups after treatment was lower than that of pretreatment(P<0.05).HOMA-IR and INS-AUC of the observation group were lower than those of the control group and pre-treatment(P<0.05).Conclusion:The treatment of PCOS-IR patients with Bushen Huatan Huoxue Recipe combined with acupuncture can improve the sex hormone,glucose metabolism level and insulin resistance.展开更多
Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with ...Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA<sub>1</sub>C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.展开更多
Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM)...Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM).Methods:Baseline data were collected from 58 patients with GDM and 51 healthy controls who were admitted Affiliated Hospital of Hebei University from May 2020 to June 2022.sSTRA5 concentrations in peripheral blood of pregnant women were measured,and SFRP-5 levels in patients with different GDM types and normal controls were analyzed by logistic regression models.Results:The levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),fasting insulin(FINS),hemoglobin A1c(HbA1c),and homeostasis model assessment-estimated insulin resistance(HOMA-IR)were higher in the observation group than in the control group,with statistically significant differences(P<0.05),while the expression levels of high-density lipoprotein cholesterol(HDL-C)and serum SFRP-5 were lower than in the control group,with statistically significant differences(P<0.05);serum SFRP-5,TG,TC,FBG,and HOMA-IR were all risk factors for GDM(P<0.05).Conclusion:Elevated serum sSTRA5 may be involved in the regulation of insulin resistance in the body and the regulation of blood glucose in the body by affecting lipid metabolism and inflammatory response.展开更多
Objective:To observe the changes in insulin resistance in patients with gestational diabetes mellitus(GDM)based on the detection of serum microRNA-372-3p and glucose transporter protein 4(GLUT4)levels.Methods:We condu...Objective:To observe the changes in insulin resistance in patients with gestational diabetes mellitus(GDM)based on the detection of serum microRNA-372-3p and glucose transporter protein 4(GLUT4)levels.Methods:We conducted a retrospective cohort study of 42 patients who were diagnosed with GDM and hospitalized in our hospital during the period from January 2017 to December 2021 and another 42 patients who had normal pregnancy during the same period by collecting their clinical data.We analyzed their serum microRNA expression profiles and miR-372-3p levels to study the relationship between GDM and insulin resistance.Results:The relative expression of miR-372-3p in the serum of patients in the GDM group was significantly higher than that of patients in the control group,but the GLUT 4 level of the GDM group was significantly lower than that of the control group(P<0.05).Compared with the control group,the GDM group had significantly higher levels of fasting blood glucose(FBG),fasting insulin(FINS),2-hour postprandial blood glucose(2h-BG),total cholesterol(TC),triglyceride(TG),and homeostatic model assessment for insulin resistance(HOMA-IR)index but significantly lower homeostasis model assessment ofβ-cell function(HOMA-β)index(P<0.05).The relative expression of miR-372-3p in serum was independently and positively correlated with HOMA-IR,while the level of GLUT4 was independently and negatively correlated with HOMA-IR(P<0.05).Conclusion:Glycosylated hemoglobin test in the early stages of pregnancy(12–13 weeks of gestation)is important to ensure the health of pregnant women and fetuses.The screening and intervention for elevated glucose in pregnant women act as a guideline for the treatment of GDM.Patients with insulin resistance and related complications such as hyperinsulinemia and hypoglycemia should be given priority.展开更多
基金supported by the European Regional Development Funds-European Union(ERDF-EU),FATZHEIMER project(EU-LAC HEALTH 2020,16/T010131 to FRdF),“Una manera de hacer Europa”Ministerio de Economía,Industria y Competitividad,Gobierno de Espa?a,Programa Estatal de Investigación,Desarrollo e Innovación Orientada a los Retos de la Sociedad(RTC2019-007329-1 to FRdF)+2 种基金Consejería de Economía,Conocimiento y Universidad,Junta de Andalucía,Plan Andaluz de Investigación,Desarrollo e Innovación(P18TP-5194 to FRdF)Instituto de Salud CarlosⅢ(DTS22/00021 to FRdF)DMV(FI20/00227)holds a“PFIS’’predoctoral contract from the National System of Health,EU-ERDF-Instituto de Salud CarlosⅢ。
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.
基金by National Natural Science Foundation of China(81803224)Young Scholars Program of Shandong University(2018WLJH33)to X.G.+3 种基金National Natural Science Foundation of China(81973031)Cheeloo Young Scholar Program of Shandong University(21320089963054)to H.W.Young Scholars Program of Shandong University(2018WLJH34)the Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology(LMDBKF-2019-05)to L.D.
文摘With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.
基金Supported by the National Natural Science Foundation of China,No.82170286Basic Research Program of Guizhou Province(Natural Sciences),No.ZK[2023]321+1 种基金Start-up Fund of Guizhou Medical University,No.J2021032Postdoctoral Research Fund of Affiliated Hospital of Guizhou Medical University,No.BSH-Q-2021-10.
文摘The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2020MH147National Natural Science Foundation of China,No.82002343.
文摘BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.
文摘Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence of insulin resistance and associated risk factors in diabetic patients in the Democratic Republic of Congo between 2005 and 2023. Method: We measured fasting blood glucose and insulin levels and looked for metabolic syndrome parameters (2009 criteria) in type 2 diabetes patients in 2005-2008 (n = 176) and in 2018-2023 (n = 303). The HOMA model was used to measure insulin sensitivity and islet β-cell secretory function. Results: Between 2005 and 2013, the trend was towards an increase in the prevalence of insulin resistance (from 13.1% to 50.8%;p Conclusion: This present study shows an increase in insulin resistance in Congolese urban areas and a persistence of atypical diabetes mellitus in Congolese rural areas, confirming the particularity of the pathophysiology of the disease in African areas currently influenced by the epidemiological transition. Further studies using an appropriate methodology are required.
文摘Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood,selenoprotein P,seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms.Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion.This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.
文摘The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.
文摘BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically studied.There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents,despite their continuous rise.AIM To investigate the association between CRF and insulin resistance in obese adolescents,with special emphasis on severely obese adolescents.METHODS We performed a prospective,cross-sectional study that included 200 pubertal adolescents,10 years to 18 years of age,who were referred to a tertiary care center due to obesity.According to body mass index(BMI),adolescents were classified as mildly obese(BMI 100% to 120% of the 95^(th)percentile for age and sex)or severely obese(BMI≥120% of the 95^(th)percentile for age and sex or≥35 kg/m^(2),whichever was lower).Participant body composition was assessed by bioelectrical impedance analysis.A homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.Maximal oxygen uptake(VO_(2)max)was determined from submaximal treadmill exercise test.CRF was expressed as VO_(2)max scaled by total body weight(TBW)(mL/min/kg TBW)or by fat free mass(FFM)(mL/min/kg FFM),and then categorized as poor,intermediate,or good,according to VO_(2)max terciles.Data were analyzed by statistical software package SPSS(IBM SPSS Statistics for Windows,Version 24.0).P<0.05 was considered statistically significant.RESULTS A weak negative correlation between CRF and HOMA-IR was found[Spearman’s rank correlation coefficient(rs)=-0.28,P<0.01 for CRF_(TBW);(r_(s))=-0.21,P<0.01 for CRF_(FFM)].One-way analysis of variance(ANOVA)revealed a significant main effect of CRF on HOMA-IR[F(2200)=6.840,P=0.001 for CRF_(TBW);F_((2200))=3.883,P=0.022 for CRF_(FFM)].Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF(P=0.001 for CRF_(TBW);P=0.018 for CRF_(FFM)).Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR[F_((2200))=3.292,P=0.039 for CRF_(TBW)].Severely obese adolescents had higher HOMA-IR than those who were mildly obese,with either good or poor CRF.However,HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF.CONCLUSION CRF is an important determinant of insulin resistance in obese adolescents,regardless of obesity category.Therefore,CRF assessment should be a part of diagnostic procedure,and its improvement should be a therapeutic goal.
基金supported by a grant from All India Institute of Medical Sciences,New Delhi (to RD and TD)Indian Council of Medical Research,Senior Research Fellowship Grant (3/1/2(24)/oph-2009-NCD-II,to MAF)+1 种基金Feldstein Medical Foundation Research Grant (to KCC)unrestricted fund from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology (to KCC)。
文摘Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.
基金supported by the National Natural Science Foundation of China(81903871)Natural Science Foundation of Jiangsu Province(BK20190565)+1 种基金Fundamental Research Funds for the Central Universities(2632021ZD16)Zhenjiang City 2022 Science and Technology Innovation Fund(SH2022084).
文摘Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.
基金funded by National Key R&D Program of China(2022YFF1100300)National Natural Science Foundation of China(31900292)+1 种基金Science and Technology Development Program of Henan Province(212102110469,222102520035)Research on Precision Nutrition and Health Food,Department of Science and Technology of Henan Province(CXJD2021006).
文摘Patrinia scabiosaefolia,is used as wild vegetable in China for more than 2000 years,with a variety of pharmacological activities,including anti-inflammatory,anti-tumor and hypoglycemic.Based on our ongoing research on chemical constituents and hypoglycemic activity of P.scabiosaefolia,4 lignan compounds,(+)-isolariciresinol(1),7R,7’R,8S,8’S-(+)-neo-olivil-4-O-β-D-glucopyranoside(2),4-O-methylcedrusin(3)and patrinian A(4),were isolated and identifi ed.The hypoglycemic activity showed that compounds 2 and 3 could extremely signifi cantly improve insulin resistance at 100(P<0.001),50(P<0.001)and 25μmol/L(P<0.01)in IR 3T3-L1 cells.While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100μmol/L(P<0.01).Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS,PI-3K,p-AKT and glucose transporter 4(GLUT4),and promoted the transcription of GLUT4 mRNA.Therefore,the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.
基金Scientific Research Project of Heilongjiang Provincial Health Commission(No.20222121020595)Traditional Chinese Medicine Research Project of Heilongjiang Province(No.ZHY2020-041)。
文摘Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.
基金Supported by National Natural Science Foundation of China(82174525)Jilin Science and Technology Development Plan Project(YDZJ202201ZYTS195)Jilin Traditional Chinese Medicine Science and Technology Project in 2022(2022128).
文摘This paper discusses the mechanism of insulin resistance in obesity from the research progress of Chinese and Western medicine and its oxidative stress,inflammatory reaction and abnormal lipid metabolism in cognitive dysfunction.It also reviews the research progress of massage,one of the external treatment methods of traditional Chinese medicine,in the treatment of insulin resistance and cognitive dysfunction in obesity,in order to provide more new ideas and new ways for clinical diagnosis and treatment of insulin resistance and related cognitive dysfunction caused by obesity.
基金Natural Science Foundation of Hubei Province (No.2020CFB858)。
文摘Objective:To investigate the clinical efficacy and effects on sex hormone level and glucose metabolism indexes of acupuncture therapy combined with the Bushen Huatan Huoxue Recipe in patients with polycystic ovary syndrome(PCOS)with insulin resistance(IR).Methods:The patients with PCOS-IR admitted from December 2021 to December 2022 were randomly divided into two groups,30 cases in each group.The comparison one and the observation one were given the relevant treatment of metformin and traditional Chinese medicine combined with acupuncture,respectively.The evidence points,sex hormone indexes and glucose metabolism indexes were compared between the two groups before and after treatment,and the insulin resistance index(HOMA-IR),glucose area under the curve(GLU-AUC)and blood insulin area under the curve(INS-AUC)were calculated.Results:The evidence points of the observation group of patients were less than the pre-treatment and comparison groups;after treatment,the follicle-stimulating hormone(FSH)level of patients in the observation group was more than the control and pre-treatment groups(P<0.05),and the ratio of luteinizing hormone(LH)to follicle-stimulating hormone(FSH)was less than that of the comparison and pre-treatment groups(P<0.05),and the levels of LH and testosterone(T)were reduced to varying degrees in both groups around the time of treatment(P<0.05).The patients in the observation group had lower levels of 0.5hPG than those in the comparison group and pretreatment(both P<0.05),and the levels of 3hPG in both groups were lower than those before treatment(P<0.05).The oral OGIRT in each of the two groups after treatment was lower than that of pretreatment(P<0.05).HOMA-IR and INS-AUC of the observation group were lower than those of the control group and pre-treatment(P<0.05).Conclusion:The treatment of PCOS-IR patients with Bushen Huatan Huoxue Recipe combined with acupuncture can improve the sex hormone,glucose metabolism level and insulin resistance.
文摘Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA<sub>1</sub>C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.
基金Youth Science and Technology Fund of Affiliated Hospital of Hebei University(Project number:2017Q024)Baoding City Science and Technology Plan Projects(Project number:2041ZF295)Hebei University Medical Subject Cultivation Project(Project number:2022B03)。
文摘Objective:To investigate the correlation between serum secretory frizzled-related protein 5(SFRP-5)expression levels and insulin resistance and glucolipid metabolism in patients with gestational diabetes mellitus(GDM).Methods:Baseline data were collected from 58 patients with GDM and 51 healthy controls who were admitted Affiliated Hospital of Hebei University from May 2020 to June 2022.sSTRA5 concentrations in peripheral blood of pregnant women were measured,and SFRP-5 levels in patients with different GDM types and normal controls were analyzed by logistic regression models.Results:The levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),fasting insulin(FINS),hemoglobin A1c(HbA1c),and homeostasis model assessment-estimated insulin resistance(HOMA-IR)were higher in the observation group than in the control group,with statistically significant differences(P<0.05),while the expression levels of high-density lipoprotein cholesterol(HDL-C)and serum SFRP-5 were lower than in the control group,with statistically significant differences(P<0.05);serum SFRP-5,TG,TC,FBG,and HOMA-IR were all risk factors for GDM(P<0.05).Conclusion:Elevated serum sSTRA5 may be involved in the regulation of insulin resistance in the body and the regulation of blood glucose in the body by affecting lipid metabolism and inflammatory response.
基金supported by the following projects:Youth Science and Technology Fund of Affiliated Hospital of Hebei University(2017Q024)Baoding City Science and Technology Plan Project(2041zf295),and Hebei University Medical Subject Cultivation Project(2022b03).
文摘Objective:To observe the changes in insulin resistance in patients with gestational diabetes mellitus(GDM)based on the detection of serum microRNA-372-3p and glucose transporter protein 4(GLUT4)levels.Methods:We conducted a retrospective cohort study of 42 patients who were diagnosed with GDM and hospitalized in our hospital during the period from January 2017 to December 2021 and another 42 patients who had normal pregnancy during the same period by collecting their clinical data.We analyzed their serum microRNA expression profiles and miR-372-3p levels to study the relationship between GDM and insulin resistance.Results:The relative expression of miR-372-3p in the serum of patients in the GDM group was significantly higher than that of patients in the control group,but the GLUT 4 level of the GDM group was significantly lower than that of the control group(P<0.05).Compared with the control group,the GDM group had significantly higher levels of fasting blood glucose(FBG),fasting insulin(FINS),2-hour postprandial blood glucose(2h-BG),total cholesterol(TC),triglyceride(TG),and homeostatic model assessment for insulin resistance(HOMA-IR)index but significantly lower homeostasis model assessment ofβ-cell function(HOMA-β)index(P<0.05).The relative expression of miR-372-3p in serum was independently and positively correlated with HOMA-IR,while the level of GLUT4 was independently and negatively correlated with HOMA-IR(P<0.05).Conclusion:Glycosylated hemoglobin test in the early stages of pregnancy(12–13 weeks of gestation)is important to ensure the health of pregnant women and fetuses.The screening and intervention for elevated glucose in pregnant women act as a guideline for the treatment of GDM.Patients with insulin resistance and related complications such as hyperinsulinemia and hypoglycemia should be given priority.
