Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome prolifera...Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.展开更多
Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes m...Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control展开更多
基金Supported by the National Natural Science Foundation of China(No.81473639)the Fundamental Research Funds for the Central Universities(No.3332018037)
文摘Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.
基金supported by Shandong Natural Science Fund(Y2008c170)
文摘Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control
文摘目的分析骨质疏松性胸腰椎压缩性骨折患者血清过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptorγcoactivator 1α,PGC-1α)、白介素-17(interleukin-17,IL-17)表达水平及其与骨代谢的关系。方法将2014年1月至2019年4月湖北省中西医结合医院诊治的58例骨质疏松性胸腰椎压缩性骨折患者纳入骨折组,将该院同期67例单纯骨质疏松患者纳入骨质疏松组,将该院同期62例体检健康者纳入健康对照组。比较三组研究对象血清PGC-1α、IL-17表达水平,并分析其与骨代谢标志物——Ⅰ型前胶原氨基端前肽(N-terminal propeptide of typeⅠprocollagen,PINP)、骨钙素(osteocalcin,OCN)、Ⅰ型胶原羟基端肽β降解产物(β-isomerised C-terminal telopeptide of collagen typeⅠ,β-CTX)、25-羟维生素D[25-hydroxy vitamin D,25(OH)D]、甲状旁腺激素(parathyroid hormone,PTH)之间的相关性,评估PGC-1α、IL-17对骨质疏松性胸腰椎压缩性骨折的预测价值。结果三组研究对象血清PGC-1α、25(OH)D水平依次为:骨折组<骨质疏松组<健康对照组(均P<0.05),IL-17、PINP、OCN、β-CTX和PTH水平依次为:骨折组>骨质疏松组>健康对照组(均P<0.05)。Pearson相关性分析显示,PGC-1α水平与PINP、OCN、β-CTX、PTH水平均呈负相关(均P<0.01),与25(OH)D水平呈正相关(P<0.01);IL-17水平与PINP、OCN、β-CTX、PTH水平均呈正相关(均P<0.01),与25(OH)D水平呈负相关(P<0.01)。受试者操作特征曲线显示,PGC-1α、IL-17对骨质疏松性胸腰椎压缩性骨折具有一定的预测价值[曲线下面积(area under the curve,AUC)=0.887、0.835],且两项指标联合的预测价值更高(AUC=0.948)。结论PGC-1α、IL-17与骨代谢关系密切,可能参与骨质疏松性胸腰椎压缩性骨折的病理生理过程,且两项指标联合检测对骨质疏松性胸腰椎压缩性骨折具有更好的预测价值。