BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to hum...BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.展开更多
AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar...AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.展开更多
Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amylolique...Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.展开更多
Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common ...Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function,and can therefore also be used to reflect whole-brain structural changes related to T2 DM.A total of 136 participants(64 men and 72 women,aged 55–86 years) were recruited for our study between January 2014 and December 2016.All participants underwent MRI and Mini-Mental State Examination assessment(including 42 healthy control,38 T2 DM without cognitive impairment,26 with cognitive impairment but without T2 DM,and 30 T2 DM with cognitive impairment participants).The total and sub-category brain atrophy and lesion index scores in patients with T2 DM with cognitive impairment were higher than those in healthy controls.Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2 DM patients with cognitive impairment and patients with T2 DM and cognitive impairment.After adjusting for age,the brain atrophy and lesion index retained its capacity to identify patients with T2 DM with cognitive impairment.These findings suggest that the brain atrophy and lesion index,based on T1-weighted and T2-weighted imaging,is of clinical value for identifying patients with T2 DM and cognitive impairment.Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2 DM that is complicated by cognitive impairment.This study was approved by the Medical Ethics Committee of University of South China(approval No.USC20131109003) on November 9,2013,and was retrospectively registered with the Chinese Clinical Trial Registry(registration No.Chi CTR1900024150) on June 27,2019.展开更多
Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new thera...Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.展开更多
Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the num...Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.展开更多
Biological molecules could be used as risk assessment tools for predicting incident Type 2Diabetes Mellitas(T2DM),such as microR NAs(mi RNAs).Numerous studies have shown association between miR NA and susceptibility o...Biological molecules could be used as risk assessment tools for predicting incident Type 2Diabetes Mellitas(T2DM),such as microR NAs(mi RNAs).Numerous studies have shown association between miR NA and susceptibility of T2DM,suggesting that mi RNAs might be common biological factors for T2DM.Interestingly,miR NAs could also serve as novel biomarkers for T2DM展开更多
Objective: To investigate the potential comorbidity biomarkers for Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD). Methods: This is a randomized case-control study. There are three groups: 1) normal con...Objective: To investigate the potential comorbidity biomarkers for Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD). Methods: This is a randomized case-control study. There are three groups: 1) normal control group included 32 healthy elderly people in the hospital physical examination;2) 30 patients with T2DM group;and 3) AD group has 28 cases. On-line reversed-phase liquid chromatography separation, tandem mass spectrometry analysis and iTRAQ quantification were used for identification of peptidomic analysis, then detection of three comorbidity biomarkers might be associated with T2DM and AD by ELISA. Results: The Peptidomic Analysis of the potential comorbidity biomarkers for T2DM and the AD group includes Osteopontin (OPN), Isoform 2 of Histone H2Btype 2-F and Histone H4. These potential comorbidity biomarkers for T2DM and the AD group are significantly increased than normal control group. OPN concentrations are 1.67 (0.13 - 2.63) mmol/L in the normal control group, 3.15 (1.51 - 5.35) mmol/L in the T2DM group, and 7.66 (3.55 - 15.38) mmol/L in the AD group. Histone H4 concentrations in three groups respectively are 0.21 ± 0.036 mmol/L (normal control), 0.21 ± 0.046 mmol/L (T2DM) and 0.21 ± 0.034 mmol/L(AD). Isoforms 2 of Histone H2Btype 2-F are 1.73 (0.12 - 2.60) mmol/L, 4.71 (1.26 - 6.84) mmol/L and 9.30 (0 - 20.8) mmol/Lin three groups respectively. Conclusion: The inflammatory mechanism may lead to an increase of histone content in the urine of AD and T2DM patients. Clinical test of these potential comorbidity biomarkers Histones and Osteopontin would be the diagnosis of comorbidity AD and T2DM.展开更多
Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure a...Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure and chronic renal dialysis. Genetic susceptibility has been implicated in DKD. The angiotensin converting enzyme (ACE) is one of the key roles in the renin angiotensin system cascade by converting angiotensin I to angiotensin II which plays a key role in regulation of blood pressure as well as electrolytes and fluid balance. This study addressed the association of (ACE) gene polymorphisms with DN in Egyptian (T2DM) patients. Methods: Our research comprised of 75 cases of T2DM with diabetic kidney disease, 100 cases of T2DM without DKD and 94 healthy volunteers. Different genotypes of ACE gene were determined by SSP-PCR analysis. Results: Gene polymorphism of ACE (DD, ID, II) in diabetic patient with DKD is 44%, 52%, 4% respectively and for T2DM individuals without DKD is 23%, 72%, 5% respectively. (DD) had significant higher frequencies in T2DM patients with DKD compared to those without DKD (p < 0.005) and (ID) had significant higher frequencies in T2DM without DKD (p < 0.0001). These results indicated that there is an association between ACE gene polymorphisms and susceptibility of diabetic patients to be affected by diabetic kidney disease. Conclusion: From our results, we can conclude that genotype of ACE in Egypt DD is the genotype of cases diabetic kidney disease. So the presence of D allele has a significant relation with diabetic kidney disease. Our data confirm the role of ACE in its relationship with diabetic kidney disease in Egyptian type 2 diabetic patients.展开更多
Background: The aim of the current study was to evaluate the anthropometric and demographic factors and their correlation with type 2 diabetes mellitus (T2DM) in Bangladesh. Methods: One hundred fourteen patients (70 ...Background: The aim of the current study was to evaluate the anthropometric and demographic factors and their correlation with type 2 diabetes mellitus (T2DM) in Bangladesh. Methods: One hundred fourteen patients (70 males and 44 females) between 30 and 75 years of age from various areas of Bangladesh were screened for T2DM. Fasting blood sugar (FBS) was analyzed by using laboratory kits and spectrophotometric technique. Anthropometric and socio-demographic data were collected using a structured questionnaire. Body mass index (BMI) was calculated from weight (kg) and height (m) of the individual respondents. Physical activity was categorized based on activity during daily work. Economic condition is defined by respective family income and education level is categorized into 3 levels: illiterate, 0 - 12 years of education and graduate or above. Results: According to the current study results, half of the patients were from the middle-class family with low physical activity and their age was within the range of 30 - 45 years. The male and female ratio of the study population was 60:40. Most of the patients were found to be obese and educated. Urban populations were more prone to have DM than the rural population. Age, education, the area of residence (urban and rural), physical activity and co-morbid diseases were significantly correlated with T2DM in Bangladesh (P Conclusion: Our study shows that different socio-demographic factors have a significant correlation with T2DM in Bangladesh. Diabetes awareness, early diagnosis, patient education and life-style modification can be initiated to manage T2DM efficiently.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Type 2 diabetes mellitus is a growing health problem, characterized by insulin resistance progressing to beta cell d...<div style="text-align:justify;"> <span style="font-family:Verdana;">Type 2 diabetes mellitus is a growing health problem, characterized by insulin resistance progressing to beta cell dysfunction and insulin deficiency, most of these patients will need intensification of treatment and initiation of insulin to delay or prevent diabetic complications. Glycemic control is the most important aspect of management, and in reducing morbidity and mortality of the diseases. Control of plasma glucose in patients with diabetes can be assessed by HbA1c, FPG, PPG, but still HbA1c% remains the gold standard for assessment of glycemic control and follow up of diabetic patients. The aim of this study is to assess HbA1c% in patients on oral anti-diabetic drugs, with poor glycemic control before and after adding basal insulin, with titration of the dose of insulin depending on fasting blood sugar. 82 patients with uncontrolled type 2 diabetes (43.9% male, 56.1% female), with HbA1c more than 9%, on two types of oral diabetic medication or more, were started on basal insulin (glargine, lantus) and followed for three to six months. Overall 82 patients with type 2 diabetes mellitus were included in the study. The mean age of the study population was 58.4 years, the mean duration of the disease range was 13.4 years. All patients with HbA1c more than 9%, without organ failure, were included in the study. The mean HbA1c overall had decreased from mean of 11.15% before starting basal insulin to the mean of 8.43% within 3 to 6 month, after initiating basal insulin, this difference was significant at p < 0.001. There was no adverse effect on this medication in any of the study group. The addition of basal insulin to oral anti-diabetic medication in uncontrolled insulin-na<span style="color:#4F4F4F;font-family:"font-size:14px;white-space:normal;background-color:#F7F7F7;">ï</span>ve type 2 diabetic patients resulted in significant improvement of glycemic control, with improved HbA1c level, without adverse effects.</span> </div>展开更多
Objectives: Diabetic retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM). It is multifactorial with the contribution of multiple genetic factors. We questioned the...Objectives: Diabetic retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM). It is multifactorial with the contribution of multiple genetic factors. We questioned the association of polymorphisms in the peroxisome proliferator-activated receptor ?2 (PPAR?2) gene (Pro12Ala and C161T) with DR in an Egyptian population. Methods: This case control study included one hundred healthy individuals and 252 T2DM among them 122 with DR and 130 without DR. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The Pro12Ala Ala allele was associated with decreased risk of DR with an odds ratio (OR) of 0.484, 95% confidence interval (CI) (0.254 - 0.920), and a p value = 0.024. The C161T T allele was associated with increased risk of DR with OR = 2.593, 95% CI (1.672 - 4.020), p < 0.001. However, when considering other covariates such as glycosylated hemoglobin (HbA<sub>1c</sub>) in multivariate regression analysis only C161T was associated with increased risk of DR with OR = 3.479, 95% CI (1.907 - 6.346), p < 0.001, while the significant association with Pro12Ala was lost. HbA<sub>1c</sub> was higher in Pro/Pro genotype when compared to those with Ala/Ala and Pro/Ala genotypes. Conclusion: We report that T allele of C161T increased risk of DR in the studied population. Further studies are warranted to investigate functional implications of polymorphisms of the PPAR-? gene in DR development.展开更多
Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats...Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.展开更多
BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK...BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.展开更多
Type 2 diabetes mellitus (T2DM) accounts for 90% of all diabetes cases and results in severe complications. It is a multifactorial metabolic disorder that results from a combination of resistance to insulin action and...Type 2 diabetes mellitus (T2DM) accounts for 90% of all diabetes cases and results in severe complications. It is a multifactorial metabolic disorder that results from a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The interaction between multiple genetic and environmental determinants has been considered to contribute to the pathogenesis of T2DM[1].展开更多
Type 2 diabetes mellitus(T2DM)is a multifactorial disease caused by both genetic and environmental factors.Although many genes have been reported to be involved in T2DM,much is still unknown about other genes that are...Type 2 diabetes mellitus(T2DM)is a multifactorial disease caused by both genetic and environmental factors.Although many genes have been reported to be involved in T2DM,much is still unknown about other genes that are involved in the disease and its progression.Therefore,the exploration of new factors plays a pivotal role in the development of new methods and strategies to prevent this chronic disease.展开更多
文摘BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.
基金Supported by Russian Science Foundation,No.17-75-30052
文摘AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.
基金supported by the National Natural Science Foundation of China(32072182)。
文摘Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.
基金supported by the National Natural Science Foundation of China,No.81271538 (to SNP)345 Talent Project and the Natural Science Foundation of Liaoning Province of China,No.2019-ZD-0794 (to SNP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2017JJ2225 (to JCL),2018JJ2357 (to GHL)Hunan Provincial Science and Technology Innovation Program of China,No.2017SK50203 (to HZ)。
文摘Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function,and can therefore also be used to reflect whole-brain structural changes related to T2 DM.A total of 136 participants(64 men and 72 women,aged 55–86 years) were recruited for our study between January 2014 and December 2016.All participants underwent MRI and Mini-Mental State Examination assessment(including 42 healthy control,38 T2 DM without cognitive impairment,26 with cognitive impairment but without T2 DM,and 30 T2 DM with cognitive impairment participants).The total and sub-category brain atrophy and lesion index scores in patients with T2 DM with cognitive impairment were higher than those in healthy controls.Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2 DM patients with cognitive impairment and patients with T2 DM and cognitive impairment.After adjusting for age,the brain atrophy and lesion index retained its capacity to identify patients with T2 DM with cognitive impairment.These findings suggest that the brain atrophy and lesion index,based on T1-weighted and T2-weighted imaging,is of clinical value for identifying patients with T2 DM and cognitive impairment.Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2 DM that is complicated by cognitive impairment.This study was approved by the Medical Ethics Committee of University of South China(approval No.USC20131109003) on November 9,2013,and was retrospectively registered with the Chinese Clinical Trial Registry(registration No.Chi CTR1900024150) on June 27,2019.
文摘Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.
文摘Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.
基金supported by grants from National Natural Science Foundation of China[81370083,81673247]Australian-China Collaborative Grant[NH&MRC-APP1112767-NSFC 81561128020]
文摘Biological molecules could be used as risk assessment tools for predicting incident Type 2Diabetes Mellitas(T2DM),such as microR NAs(mi RNAs).Numerous studies have shown association between miR NA and susceptibility of T2DM,suggesting that mi RNAs might be common biological factors for T2DM.Interestingly,miR NAs could also serve as novel biomarkers for T2DM
文摘Objective: To investigate the potential comorbidity biomarkers for Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD). Methods: This is a randomized case-control study. There are three groups: 1) normal control group included 32 healthy elderly people in the hospital physical examination;2) 30 patients with T2DM group;and 3) AD group has 28 cases. On-line reversed-phase liquid chromatography separation, tandem mass spectrometry analysis and iTRAQ quantification were used for identification of peptidomic analysis, then detection of three comorbidity biomarkers might be associated with T2DM and AD by ELISA. Results: The Peptidomic Analysis of the potential comorbidity biomarkers for T2DM and the AD group includes Osteopontin (OPN), Isoform 2 of Histone H2Btype 2-F and Histone H4. These potential comorbidity biomarkers for T2DM and the AD group are significantly increased than normal control group. OPN concentrations are 1.67 (0.13 - 2.63) mmol/L in the normal control group, 3.15 (1.51 - 5.35) mmol/L in the T2DM group, and 7.66 (3.55 - 15.38) mmol/L in the AD group. Histone H4 concentrations in three groups respectively are 0.21 ± 0.036 mmol/L (normal control), 0.21 ± 0.046 mmol/L (T2DM) and 0.21 ± 0.034 mmol/L(AD). Isoforms 2 of Histone H2Btype 2-F are 1.73 (0.12 - 2.60) mmol/L, 4.71 (1.26 - 6.84) mmol/L and 9.30 (0 - 20.8) mmol/Lin three groups respectively. Conclusion: The inflammatory mechanism may lead to an increase of histone content in the urine of AD and T2DM patients. Clinical test of these potential comorbidity biomarkers Histones and Osteopontin would be the diagnosis of comorbidity AD and T2DM.
文摘Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure and chronic renal dialysis. Genetic susceptibility has been implicated in DKD. The angiotensin converting enzyme (ACE) is one of the key roles in the renin angiotensin system cascade by converting angiotensin I to angiotensin II which plays a key role in regulation of blood pressure as well as electrolytes and fluid balance. This study addressed the association of (ACE) gene polymorphisms with DN in Egyptian (T2DM) patients. Methods: Our research comprised of 75 cases of T2DM with diabetic kidney disease, 100 cases of T2DM without DKD and 94 healthy volunteers. Different genotypes of ACE gene were determined by SSP-PCR analysis. Results: Gene polymorphism of ACE (DD, ID, II) in diabetic patient with DKD is 44%, 52%, 4% respectively and for T2DM individuals without DKD is 23%, 72%, 5% respectively. (DD) had significant higher frequencies in T2DM patients with DKD compared to those without DKD (p < 0.005) and (ID) had significant higher frequencies in T2DM without DKD (p < 0.0001). These results indicated that there is an association between ACE gene polymorphisms and susceptibility of diabetic patients to be affected by diabetic kidney disease. Conclusion: From our results, we can conclude that genotype of ACE in Egypt DD is the genotype of cases diabetic kidney disease. So the presence of D allele has a significant relation with diabetic kidney disease. Our data confirm the role of ACE in its relationship with diabetic kidney disease in Egyptian type 2 diabetic patients.
文摘Background: The aim of the current study was to evaluate the anthropometric and demographic factors and their correlation with type 2 diabetes mellitus (T2DM) in Bangladesh. Methods: One hundred fourteen patients (70 males and 44 females) between 30 and 75 years of age from various areas of Bangladesh were screened for T2DM. Fasting blood sugar (FBS) was analyzed by using laboratory kits and spectrophotometric technique. Anthropometric and socio-demographic data were collected using a structured questionnaire. Body mass index (BMI) was calculated from weight (kg) and height (m) of the individual respondents. Physical activity was categorized based on activity during daily work. Economic condition is defined by respective family income and education level is categorized into 3 levels: illiterate, 0 - 12 years of education and graduate or above. Results: According to the current study results, half of the patients were from the middle-class family with low physical activity and their age was within the range of 30 - 45 years. The male and female ratio of the study population was 60:40. Most of the patients were found to be obese and educated. Urban populations were more prone to have DM than the rural population. Age, education, the area of residence (urban and rural), physical activity and co-morbid diseases were significantly correlated with T2DM in Bangladesh (P Conclusion: Our study shows that different socio-demographic factors have a significant correlation with T2DM in Bangladesh. Diabetes awareness, early diagnosis, patient education and life-style modification can be initiated to manage T2DM efficiently.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Type 2 diabetes mellitus is a growing health problem, characterized by insulin resistance progressing to beta cell dysfunction and insulin deficiency, most of these patients will need intensification of treatment and initiation of insulin to delay or prevent diabetic complications. Glycemic control is the most important aspect of management, and in reducing morbidity and mortality of the diseases. Control of plasma glucose in patients with diabetes can be assessed by HbA1c, FPG, PPG, but still HbA1c% remains the gold standard for assessment of glycemic control and follow up of diabetic patients. The aim of this study is to assess HbA1c% in patients on oral anti-diabetic drugs, with poor glycemic control before and after adding basal insulin, with titration of the dose of insulin depending on fasting blood sugar. 82 patients with uncontrolled type 2 diabetes (43.9% male, 56.1% female), with HbA1c more than 9%, on two types of oral diabetic medication or more, were started on basal insulin (glargine, lantus) and followed for three to six months. Overall 82 patients with type 2 diabetes mellitus were included in the study. The mean age of the study population was 58.4 years, the mean duration of the disease range was 13.4 years. All patients with HbA1c more than 9%, without organ failure, were included in the study. The mean HbA1c overall had decreased from mean of 11.15% before starting basal insulin to the mean of 8.43% within 3 to 6 month, after initiating basal insulin, this difference was significant at p < 0.001. There was no adverse effect on this medication in any of the study group. The addition of basal insulin to oral anti-diabetic medication in uncontrolled insulin-na<span style="color:#4F4F4F;font-family:"font-size:14px;white-space:normal;background-color:#F7F7F7;">ï</span>ve type 2 diabetic patients resulted in significant improvement of glycemic control, with improved HbA1c level, without adverse effects.</span> </div>
文摘Objectives: Diabetic retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM). It is multifactorial with the contribution of multiple genetic factors. We questioned the association of polymorphisms in the peroxisome proliferator-activated receptor ?2 (PPAR?2) gene (Pro12Ala and C161T) with DR in an Egyptian population. Methods: This case control study included one hundred healthy individuals and 252 T2DM among them 122 with DR and 130 without DR. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The Pro12Ala Ala allele was associated with decreased risk of DR with an odds ratio (OR) of 0.484, 95% confidence interval (CI) (0.254 - 0.920), and a p value = 0.024. The C161T T allele was associated with increased risk of DR with OR = 2.593, 95% CI (1.672 - 4.020), p < 0.001. However, when considering other covariates such as glycosylated hemoglobin (HbA<sub>1c</sub>) in multivariate regression analysis only C161T was associated with increased risk of DR with OR = 3.479, 95% CI (1.907 - 6.346), p < 0.001, while the significant association with Pro12Ala was lost. HbA<sub>1c</sub> was higher in Pro/Pro genotype when compared to those with Ala/Ala and Pro/Ala genotypes. Conclusion: We report that T allele of C161T increased risk of DR in the studied population. Further studies are warranted to investigate functional implications of polymorphisms of the PPAR-? gene in DR development.
基金Shahhag, Dhaka. Bangladesh, for providing technical moral ami financial support for this project
文摘Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.
基金National Natural Science Foundation of China,No.81603574 and No.81774286National Key Research and Development Program,No.2018YFC1704202 and No.2020YFE0201800+1 种基金University Scientific Research Projects of Anhui,No.KJ2020A0401 and No.KJ2019A0442Province Science Foundation of Anhui,No.1708085QH213.
文摘BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.
基金supported by grants from the National Natural Science Foundation of China[81573151,81872626,and81573243]Science and Technology Foundation for Innovation Talent of Henan Province[154200510010]Dietary Nutrition Research and Education Foundation of Danone[DIC2013-06]
文摘Type 2 diabetes mellitus (T2DM) accounts for 90% of all diabetes cases and results in severe complications. It is a multifactorial metabolic disorder that results from a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The interaction between multiple genetic and environmental determinants has been considered to contribute to the pathogenesis of T2DM[1].
基金This research was supported by the National Natural Science Foundation of China(No.31025019)Innovation Team Development of the Ministry of Education of China(Grant No.IRT0967).
基金supported by the National Natural Science Foundation of China[Grants 81300702 to ZLL,81501199to WC]the Natural Scienceof Chongqing CSTC[cstc2018jcyj AXO210 to ZLL and cstc2017jcyj AX0016 to WC]。
文摘Type 2 diabetes mellitus(T2DM)is a multifactorial disease caused by both genetic and environmental factors.Although many genes have been reported to be involved in T2DM,much is still unknown about other genes that are involved in the disease and its progression.Therefore,the exploration of new factors plays a pivotal role in the development of new methods and strategies to prevent this chronic disease.
