特立帕肽通过cAMP/PKA/CREB信号通路调控高糖微环境下的成骨细胞分化

目的 探讨特立帕肽对高糖微环境下小鼠胚胎成骨细胞（MC3T3-E1）分化的影响及作用机制。方法 将MC3T3-E1细胞分为正常糖组（NG,5.5 mmol/L葡萄糖）、NG+特立帕肽组（5.5 mmol/L葡萄糖+10 nmol/L特立帕肽）、高糖组（HG,25 mmol/L葡萄糖）、HG+特立帕肽组（25 mmol/L葡萄糖+10 nmol/L特立帕肽）和HG+特立帕肽+PKA抑制剂组（25 mmol/L葡萄糖+10 nmol/L特立帕肽+20μmol/L H-89）。CCK-8法检测细胞增殖;ELISA实验检测各组cAMP水平;试剂盒检测碱性磷酸酶（ALP）活性;茜素红染色检测细胞矿化结节生成情况;鬼笔环肽染色后观察细胞骨架;Real-time PCR检测细胞中PKA、CREB、RUNX2和Osx的mRNA表达水平。结果 各组细胞增殖能力差异无统计学意义（P>0.05）。与NG组相比,NG+特立帕肽组细胞cAMP水平升高（P<0.05）,ALP活性增强（P<0.05）,茜素红矿化结节生成能力增强（P<0.05）,细胞骨架清晰程度有所提升,PKA、CREB、R...     

Role of AMPK in pancreatic beta cell function

Pharmacological activation of AMP activated kinase (AMPK) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes. Despite improved glucose regulation achieved by administration of small molecule activators of AMPK, the potential negative impact of enhanced AMPK activity on insulin secretion by the pancreatic beta cell is an important consideration. In this review, we discuss our current understanding of the role of AMPK in central functions of the pancreatic beta cell, including glucose-stimulated insulin secretion (GSIS), proliferation, and survival. In addition we discuss the controversy surrounding the role of AMPK in insulin secretion, underscoring the merits and caveats of methods used to date.     

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.

银杏内酯通过激活Nrf2和CREB核转位促进抗氧化和抗凋亡基因表达发挥抗脑缺血再灌注损伤作用

目的研究银杏二萜内酯葡胺注射液(DGMI)抗大鼠脑缺血再灌注损伤的作用及机制。方法建立大鼠脑缺血再灌注损伤模型,缺血1.5 h,再灌注24 h后对神经行为学缺损程度评分,TTC测定大鼠脑梗死体积,Western印迹和免疫荧光测定大鼠脑组织中蛋白表达。结果 DGMI能够显著改善脑缺血再灌注损伤导致的大鼠神经行为学缺损症状,提高运动神经功能,减小脑梗死体积及水肿程度,抑制受损脑区的神经元凋亡。一方面,DGMI能够激活PI3K/Akt/Nrf2通路,促进Nrf2的核转位,增加HO-1蛋白的表达,提高受损脑区中Neu N与Nrf2双阳性细胞的百分比。另一方面,DGMI也能够激活PI3K/Akt/CREB通路,提高CREB磷酸化水平和受损脑区中Neu N与p-CREB双阳性细胞的百分比。结论 DGMI通过激活PI3K/Akt/Nrf2和PI3K/Akt/CREB通路共同发挥抗脑缺血再灌注损伤作用。