Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
Objective: To investigate the antioxidant, anti-a-glucosidase and pancreatic b-cell protective potential of Ensete superbum(E. superbum) seeds.Methods: A variety of in vitro assays including radical scavenging, reduci...Objective: To investigate the antioxidant, anti-a-glucosidase and pancreatic b-cell protective potential of Ensete superbum(E. superbum) seeds.Methods: A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, a-glucosidase assay and pancreatic b-cell(1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds.Results: The radical scavenging and reducing power effects comparable with the standard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of(38.2 ± 1.8)(n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin.Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic b-cell protection.展开更多
AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotoc...AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotocin(STZ).HFD was used to induce diabetes recurrence at 4 wk postoperatively.Body weight,oral glucose tolerance test,homeostatic model assessment of insulin resistance(HOMA-IR),insulin signaling[IR,insulin receptor substrate(IRS 1,IRS2,phosphatidylinositol3-kinase and AKT in liver and skeletal muscle],oral glucose stimulated insulin secretion,beta-cell morphology(mass,apoptosis and insulin secretion),glucagon-like peptide(GLP)-1,PYY and ghrelin were compared among SG rats with common low-fat diet(SG-LFD),SG with HFD(SG-HFD),DJB rats with LFD(DJB-LFD),DJB with HFD(DJB-HFD)and shamoperation with LFD(Sham)at targeted postoperative times.RESULTS SG and DJB resulted in significant improvement in glucose tolerance,lower HOMA-IR,up-regulated hepatic and muscular insulin signaling,higher levels of oral glucose-stimulated insulin secretion,bigger betacell mass,higher immunofluorescence intensity of insulin,fewer transferase-mediated d UTP-biotin 3’nick end-labeling(TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group.The improvement in glucose tolerance was reversed at 12 wk postoperatively.Compared with the SG-LFD and DJB-LFD groups,the SG-HFD and DJB-HFD groups showed higher HOMA-IR,down-regulated hepatic and muscular insulin signaling,and more TUNEL-positive beta cells.No significant difference was detected between HFD and LFD groups for body weight,glucose-stimulated insulin secretion,betacell mass,immunofluorescence intensity of insulin,and postprandial GLP-1 and PYY levels.Fasting serum ghrelin decreased in SG groups,and there was no difference between HFD-SG and LFD-SG groups.CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB.Diabetes recurrence may correlate with re-impaired insulin sensitivity,but not with alterations of beta-cell function and body weight.展开更多
Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell ...Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell function(BCF)with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.Methods:A cross-sectional survey of 15,928 participants was conducted.Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF.A restricted cubic spline(RCS)nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.Results:High triglyceride(TG),low high-density lipoprotein cholesterol,and high low-density lipoprotein cholesterol(LDL-C)accounted for 49.7%,47.8%,and 59.2%of the participants,respectively.In multivariable analysis,high IR was associated with an increased risk of high TGs(P for trend<0.001)in T1DM and is associated with an elevated risk of high TG and low HDL-C(all P for trend<0.01)in T2DM.Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.Conclusion:High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients,suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.展开更多
The concentration of free zinc within insulin-storing vesicles is important for vesicle maturity and therefore requires accurate measurement.However,common small-molecule intensity-based probes and most available gene...The concentration of free zinc within insulin-storing vesicles is important for vesicle maturity and therefore requires accurate measurement.However,common small-molecule intensity-based probes and most available genetically encoded Forster resonance energy transfer(FRET)-based sensors for zinc are unsuitable for estimating the free zinc concentration in insulin-storing vesicles.Therefore,we have developed a novel FRET-based zinc sensor based on the RING motif of TRIM72,referred to as ZnT72 R,which has an approximate K_d that varies from 6.07±0.28 μmol/L to 7.84±0.42μmol/L in vitro and a cytosol-calibrated K_d of approximately 55.56±4.59μmol/L in HEK293T cells.To pinpoint the free zinc concentration of insulin-storing vesicles,we initially targeted ZnT72R to beta-cell vesicles by fu sing them to NPY(neuropeptide Y).Following NPY-ZnT72R labeling,the FRET intensity ratios of vesicles were quantified.We found that the free zinc concentration in insulin-storing vesicles of diabetic db/db mice(28.30±1.33μmol/L) was significantly lower than that of control mice(41.46±3.53μmol/L).展开更多
Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用...目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用甘精胰岛素进行治疗,观察组则采用甘精胰岛素联合利拉鲁肽进行治疗。比较两组治疗前后的血糖检测指标、胰岛功能指标[胰岛素抵抗指数(homeostatic model assessment of insulin resistance index,HOMA-IR)及胰岛β细胞功能指数(homeostatic model assessment of β-cell function,HOMA-β)]及脂代谢相关指标。结果 治疗前,两组的血糖检测指标、胰岛β细胞功能指标及脂代谢相关指标比较,差异无统计学意义(P>0.05)。治疗3个月后,观察组的血糖检测指标、HOMA-IR、瘦素及血脂指标显著低于对照组,血清脂联素及HOMA-β显著高于对照组,且两组的检测结果显著优于治疗前,差异有统计学意义(P<0.05)。结论 甘精胰岛素联合利拉鲁肽对2型糖尿病患者中的应用效果较好,且可显著改善胰岛β细胞功能及脂代谢状态,因此在2型糖尿病患者中的应用价值较高。展开更多
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
基金Supported by a local grant from the University of Greenwich(GRE Mini-Proof-of-Concept No.HEIF-Po C-SCI-02/13)
文摘Objective: To investigate the antioxidant, anti-a-glucosidase and pancreatic b-cell protective potential of Ensete superbum(E. superbum) seeds.Methods: A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, a-glucosidase assay and pancreatic b-cell(1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds.Results: The radical scavenging and reducing power effects comparable with the standard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of(38.2 ± 1.8)(n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin.Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic b-cell protection.
基金Supported by National Natural Science Foundation of China,No.81300286 to Liu SZ and No.81471019 to Hu SYFoundation for Outstanding Young Scientist in Shandong Province,No.BS2013YY031 to Liu SZ+1 种基金Science and Technology Development Program of Shandong Province,No.2014GGE27485 to Liu SZSpecialized Research Fund for the Doctoral Program of Higher Education of China,No.20130131120069 to Liu SZ
文摘AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotocin(STZ).HFD was used to induce diabetes recurrence at 4 wk postoperatively.Body weight,oral glucose tolerance test,homeostatic model assessment of insulin resistance(HOMA-IR),insulin signaling[IR,insulin receptor substrate(IRS 1,IRS2,phosphatidylinositol3-kinase and AKT in liver and skeletal muscle],oral glucose stimulated insulin secretion,beta-cell morphology(mass,apoptosis and insulin secretion),glucagon-like peptide(GLP)-1,PYY and ghrelin were compared among SG rats with common low-fat diet(SG-LFD),SG with HFD(SG-HFD),DJB rats with LFD(DJB-LFD),DJB with HFD(DJB-HFD)and shamoperation with LFD(Sham)at targeted postoperative times.RESULTS SG and DJB resulted in significant improvement in glucose tolerance,lower HOMA-IR,up-regulated hepatic and muscular insulin signaling,higher levels of oral glucose-stimulated insulin secretion,bigger betacell mass,higher immunofluorescence intensity of insulin,fewer transferase-mediated d UTP-biotin 3’nick end-labeling(TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group.The improvement in glucose tolerance was reversed at 12 wk postoperatively.Compared with the SG-LFD and DJB-LFD groups,the SG-HFD and DJB-HFD groups showed higher HOMA-IR,down-regulated hepatic and muscular insulin signaling,and more TUNEL-positive beta cells.No significant difference was detected between HFD and LFD groups for body weight,glucose-stimulated insulin secretion,betacell mass,immunofluorescence intensity of insulin,and postprandial GLP-1 and PYY levels.Fasting serum ghrelin decreased in SG groups,and there was no difference between HFD-SG and LFD-SG groups.CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB.Diabetes recurrence may correlate with re-impaired insulin sensitivity,but not with alterations of beta-cell function and body weight.
基金National Science and Technology Infrastructure Program(Nos. 2013BAI09B12, 2015BAI12B13)National Key R&D Program of China(Nos. 2016YFC1305000, 2017YFC1309604)
文摘Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell function(BCF)with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.Methods:A cross-sectional survey of 15,928 participants was conducted.Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF.A restricted cubic spline(RCS)nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.Results:High triglyceride(TG),low high-density lipoprotein cholesterol,and high low-density lipoprotein cholesterol(LDL-C)accounted for 49.7%,47.8%,and 59.2%of the participants,respectively.In multivariable analysis,high IR was associated with an increased risk of high TGs(P for trend<0.001)in T1DM and is associated with an elevated risk of high TG and low HDL-C(all P for trend<0.01)in T2DM.Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.Conclusion:High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients,suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.
基金supported by a China Postdoctoral Science Foundation-funded project(No.2017M612440)。
文摘The concentration of free zinc within insulin-storing vesicles is important for vesicle maturity and therefore requires accurate measurement.However,common small-molecule intensity-based probes and most available genetically encoded Forster resonance energy transfer(FRET)-based sensors for zinc are unsuitable for estimating the free zinc concentration in insulin-storing vesicles.Therefore,we have developed a novel FRET-based zinc sensor based on the RING motif of TRIM72,referred to as ZnT72 R,which has an approximate K_d that varies from 6.07±0.28 μmol/L to 7.84±0.42μmol/L in vitro and a cytosol-calibrated K_d of approximately 55.56±4.59μmol/L in HEK293T cells.To pinpoint the free zinc concentration of insulin-storing vesicles,we initially targeted ZnT72R to beta-cell vesicles by fu sing them to NPY(neuropeptide Y).Following NPY-ZnT72R labeling,the FRET intensity ratios of vesicles were quantified.We found that the free zinc concentration in insulin-storing vesicles of diabetic db/db mice(28.30±1.33μmol/L) was significantly lower than that of control mice(41.46±3.53μmol/L).
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
文摘目的 探究甘精胰岛素联合利拉鲁肽对2型糖尿病患者胰岛β细胞功能及脂代谢的影响。方法 选取2021年6月—2022年12月于北京市西城区展览路医院就医的80例2型糖尿病患者为研究对象,根据随机数表法分为对照组和观察组,各40例。对照组采用甘精胰岛素进行治疗,观察组则采用甘精胰岛素联合利拉鲁肽进行治疗。比较两组治疗前后的血糖检测指标、胰岛功能指标[胰岛素抵抗指数(homeostatic model assessment of insulin resistance index,HOMA-IR)及胰岛β细胞功能指数(homeostatic model assessment of β-cell function,HOMA-β)]及脂代谢相关指标。结果 治疗前,两组的血糖检测指标、胰岛β细胞功能指标及脂代谢相关指标比较,差异无统计学意义(P>0.05)。治疗3个月后,观察组的血糖检测指标、HOMA-IR、瘦素及血脂指标显著低于对照组,血清脂联素及HOMA-β显著高于对照组,且两组的检测结果显著优于治疗前,差异有统计学意义(P<0.05)。结论 甘精胰岛素联合利拉鲁肽对2型糖尿病患者中的应用效果较好,且可显著改善胰岛β细胞功能及脂代谢状态,因此在2型糖尿病患者中的应用价值较高。
