Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates School of Forensic and Investigative Sciences, University of Central Lancashire, Preston, England PR1 2HE, UK Hormones Department, National Research Centre, Cairo, Egypt School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, England PR1 2HE, UK Departments of Anatomy Medical Microbiology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates.
J Endocrinol. 2014 Feb 10;220(3):291-304. doi: 10.1530/JOE-13-0426. Print 2014 Mar.
Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes. The results show that exenatide improved BW gain and reduced blood glucose in diabetic rats compared with controls. Similarly, exenatide enhanced insulin release from the pancreatic fragments and improved liver and kidney functions and lipid profile in diabetic rats compared with controls. Exenatide not only induced significant increases in serum insulin level but also elevated the number of insulin-, GLP1- and exenatide-positive cells compared with untreated controls. Exenatide also elevated the number of catalase- and glutathione reductase-positive cells in diabetic rat pancreas compared with controls. Exenatide caused significant elevation in the expressions of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP1 receptor genes in the pancreas of both control and diabetic rats compared with untreated animals. The results have demonstrated that exenatide can exert its beneficial and protective effects by elevating the levels of endogenous antioxidants and genes responsible for the survival, regeneration and proliferation of pancreatic β-cell.
胰高血糖素样肽 1（GLP1）激动剂在治疗糖尿病方面是很有前途的治疗药物。本研究采用四组各 10 只大鼠，其中两组为链脲佐菌素诱导的糖尿病大鼠，两组为对照组，研究了 exenatide 在实验性糖尿病中的保护作用机制。对照组和糖尿病组各有一只接受 exenatide（1μg/kg 体重（BW））治疗 10 周。采集血浆进行生化分析，同时采集胰腺组织进行免疫荧光和免疫电镜研究以及实时 PCR，以检测基因的表达。结果表明，与对照组相比，exenatide 改善了糖尿病大鼠的 BW 增加和血糖降低。同样，与对照组相比，exenatide 增强了糖尿病大鼠胰腺片段的胰岛素释放，并改善了肝肾功能和脂谱。exenatide 不仅显著增加了血清胰岛素水平，而且与未治疗的对照组相比，还增加了胰岛素、GLP1 和 exenatide 阳性细胞的数量。与对照组相比，exenatide 还增加了糖尿病大鼠胰腺中过氧化氢酶和谷胱甘肽还原酶阳性细胞的数量。与未治疗的动物相比，exenatide 使胰腺十二指肠同源盒-1、热休克蛋白-70、谷胱甘肽过氧化物酶、胰岛素受体和 GLP1 受体基因在对照组和糖尿病大鼠的胰腺中的表达显著升高。结果表明，exenatide 通过提高内源性抗氧化剂和负责胰腺β细胞存活、再生和增殖的基因水平发挥其有益和保护作用。
