Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relations...Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.展开更多
AIM: To investigate the relationship of iron indices with diabetes mellitus(DM) in those without hemochromatosis.METHODS: This cross-sectional study examined data collected during the Third National Health and Nutriti...AIM: To investigate the relationship of iron indices with diabetes mellitus(DM) in those without hemochromatosis.METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey(NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included(n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated.RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects(P = 0.0001 to< 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement(P = 0.03 to< 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity(P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration(P = 0.02 to< 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance.CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2diabetes through its effect on liver function.展开更多
目的探讨初诊肥胖2型糖尿病患者血清Betatrophin水平与胰岛β细胞功能的关系。方法方便选择2014年1月—2015年1月初诊肥胖2型糖尿病患者100例为研究对象(观察组),另选择同期该院体检健康者(NGT)者100名为对照观察(对照组)。测量人体指标...目的探讨初诊肥胖2型糖尿病患者血清Betatrophin水平与胰岛β细胞功能的关系。方法方便选择2014年1月—2015年1月初诊肥胖2型糖尿病患者100例为研究对象(观察组),另选择同期该院体检健康者(NGT)者100名为对照观察(对照组)。测量人体指标,检测相关代谢血生化指标,采用酶联免疫吸附实验(ELISA)法测定空腹血清Betatrophin水平,采用直线相关分析研究betatrophin与胰岛β细胞功能、体测及代谢指标的相关关系。结果观察组血清Betatrophin水平(422.5±247.60)pg/m L明显高于对照组(316.3±293.30)pg/m L,差异有统计学意义(P<0.05);相关性分析提示Betatrophin与腰臀比、HOMA-IR、FPG、2 h PG、HbA1c、FINS、TG呈正相关(r=0.215、0.216、0.249、0.447、0.338、0.452、0.470,P<0.01),与HDL-C、HOMA-β成负相关(r=-0.256、-0.363,P<0.05),差异有统计学意义(P<0.05)。结论初诊肥胖2型糖尿病患者的血清betatrophin水平较NGT组明显升高,并且与胰岛β细胞功能密切相关,推测其参与了糖尿病的发生。展开更多
目的探讨妊娠糖尿病(GDM)患者空腹血清Apelin-36水平变化及其与临床指标的相关性。方法选取妊娠24~28周孕妇90例,根据口服葡萄糖耐量试验(OGTT)结果均分为GDM组和正常糖耐量(NGT)组,并根据孕前体质量指数(BMI孕前)24 kg/m2为切割点,将GD...目的探讨妊娠糖尿病(GDM)患者空腹血清Apelin-36水平变化及其与临床指标的相关性。方法选取妊娠24~28周孕妇90例,根据口服葡萄糖耐量试验(OGTT)结果均分为GDM组和正常糖耐量(NGT)组,并根据孕前体质量指数(BMI孕前)24 kg/m2为切割点,将GDM组和NGT组分别再分为体质量正常组和超重组。采用酶联免疫吸附(ELISA)法检测各组空腹血清Apelin-36水平,同时检测各受试者三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白(LDL)及OGTT各点血糖、胰岛素和C肽等指标,并计算稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)和混合胰岛素敏感度指数(ISIcomp),分析Apelin-36与这些指标之间的关系。结果 GDM组Apelin-36水平显著高于NGT组,差异有统计学意义(P<0.05);GDM-OB组Apelin-36水平高于GDM-NW组,差异有统计学意义(P<0.05),而NGT-NW组和NGT-OB组Apelin-36水平差异无统计学意义(P>0.05)。Pearson相关分析显示,Apelin-36与BMI孕前、FPG、30 min PG、1 h PG、2 h PG、FINS、TC、HOMA-IR正相关,与HOMA-β、ISIcomp负相关。多元逐步线性回归分析显示,BMI孕前及FINS是影响Apelin-36水平的独立相关因素。结论 Apelin-36与胰岛素抵抗正相关,与胰岛细胞功能负相关,提示其可能与GDM的发病有一定的关联。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
Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than sub...Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D.Over the past decade and a half,a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease.While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism,a few reports suggest a lack of such association.Pancreatic fat has also been linked with genetic risk of developing T2D,prediabetes,reduced insulin secretion,and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome.With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function,our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved.This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.展开更多
Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial func...Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial function and impaired Ca2＋ influx in beta cells in diabetic patients and animal models,suggesting a role for these processes in proper insulin secretion.The aim of this study was to investigate the detailed relationship of mitochondrial function,Ca2＋ influx,and defective insulin secretion.Methods We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice.Two types of Ca2＋ channel activities,L-type and store-operated Ca2＋ （SOC）,were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2＋ influx was measured by a non-invasive micro-test technique （NMT）.Results Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae,and mitochondrial function decreased compared with C57BL/6J mice.Ca2＋ channel activity was increased and glucose induced Ca2＋ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2＋ influx,but not via Ca2＋ channel activity.展开更多
基金partly supported by the National Natural Science Foundation of China,No.81370448,81570725
文摘Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.
文摘AIM: To investigate the relationship of iron indices with diabetes mellitus(DM) in those without hemochromatosis.METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey(NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included(n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated.RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects(P = 0.0001 to< 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement(P = 0.03 to< 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity(P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration(P = 0.02 to< 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance.CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2diabetes through its effect on liver function.
文摘目的探讨初诊肥胖2型糖尿病患者血清Betatrophin水平与胰岛β细胞功能的关系。方法方便选择2014年1月—2015年1月初诊肥胖2型糖尿病患者100例为研究对象(观察组),另选择同期该院体检健康者(NGT)者100名为对照观察(对照组)。测量人体指标,检测相关代谢血生化指标,采用酶联免疫吸附实验(ELISA)法测定空腹血清Betatrophin水平,采用直线相关分析研究betatrophin与胰岛β细胞功能、体测及代谢指标的相关关系。结果观察组血清Betatrophin水平(422.5±247.60)pg/m L明显高于对照组(316.3±293.30)pg/m L,差异有统计学意义(P<0.05);相关性分析提示Betatrophin与腰臀比、HOMA-IR、FPG、2 h PG、HbA1c、FINS、TG呈正相关(r=0.215、0.216、0.249、0.447、0.338、0.452、0.470,P<0.01),与HDL-C、HOMA-β成负相关(r=-0.256、-0.363,P<0.05),差异有统计学意义(P<0.05)。结论初诊肥胖2型糖尿病患者的血清betatrophin水平较NGT组明显升高,并且与胰岛β细胞功能密切相关,推测其参与了糖尿病的发生。
文摘目的探讨妊娠糖尿病(GDM)患者空腹血清Apelin-36水平变化及其与临床指标的相关性。方法选取妊娠24~28周孕妇90例,根据口服葡萄糖耐量试验(OGTT)结果均分为GDM组和正常糖耐量(NGT)组,并根据孕前体质量指数(BMI孕前)24 kg/m2为切割点,将GDM组和NGT组分别再分为体质量正常组和超重组。采用酶联免疫吸附(ELISA)法检测各组空腹血清Apelin-36水平,同时检测各受试者三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白(LDL)及OGTT各点血糖、胰岛素和C肽等指标,并计算稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)和混合胰岛素敏感度指数(ISIcomp),分析Apelin-36与这些指标之间的关系。结果 GDM组Apelin-36水平显著高于NGT组,差异有统计学意义(P<0.05);GDM-OB组Apelin-36水平高于GDM-NW组,差异有统计学意义(P<0.05),而NGT-NW组和NGT-OB组Apelin-36水平差异无统计学意义(P>0.05)。Pearson相关分析显示,Apelin-36与BMI孕前、FPG、30 min PG、1 h PG、2 h PG、FINS、TC、HOMA-IR正相关,与HOMA-β、ISIcomp负相关。多元逐步线性回归分析显示,BMI孕前及FINS是影响Apelin-36水平的独立相关因素。结论 Apelin-36与胰岛素抵抗正相关,与胰岛细胞功能负相关,提示其可能与GDM的发病有一定的关联。
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。
文摘Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D.Over the past decade and a half,a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease.While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism,a few reports suggest a lack of such association.Pancreatic fat has also been linked with genetic risk of developing T2D,prediabetes,reduced insulin secretion,and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome.With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function,our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved.This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.
基金This study was supported by grants from Fund of Capital Medical Development and Research （No. 2009-1020） and Tsinghua-Yue-Yuen Medical Science Foundation （No.20240000531 and No.20240000568）
文摘Background Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes.Previous studies found impaired mitochondrial function and impaired Ca2＋ influx in beta cells in diabetic patients and animal models,suggesting a role for these processes in proper insulin secretion.The aim of this study was to investigate the detailed relationship of mitochondrial function,Ca2＋ influx,and defective insulin secretion.Methods We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice.Two types of Ca2＋ channel activities,L-type and store-operated Ca2＋ （SOC）,were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2＋ influx was measured by a non-invasive micro-test technique （NMT）.Results Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae,and mitochondrial function decreased compared with C57BL/6J mice.Ca2＋ channel activity was increased and glucose induced Ca2＋ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2＋ influx,but not via Ca2＋ channel activity.
