Mechanism of the beneficial and protective effects of exenatide in diabetic rats

Abstract

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 mg/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 b-cell.

Hypoglycemic effects of Zanthoxylum alkylamides by enhancing glucose metabolism and ameliorating pancreatic dysfunction in streptozotocin-induced diabetic rats

“…The hypoglycemic properties of some bioactive components are mainly induced by protecting the pancreatic islets and by improving insulin secretion. 45,46 In the present study, following the damage of the pancreatic β-cells by STZ, the expression levels of PDX-1, GLUT2, and GK were remarkably downregulated in the pancreas. 44 During pancreas development, PDX-1 is expressed in precursor cells and then becomes restricted to β-cells.…”

Does Glucagon-like Peptide-1 Ameliorate Oxidative Stress in Diabetes? Evidence Based on Experimental and Clinical Studies

“…In diabetic Wistar rats, ten weeks of exenatide treatment initiated five days after STZ exposure led to decreased blood glucose levels after four and eight weeks and improved glucose tolerance as measured by intraperitoneal glucose tolerance test (IPGTT) at the end of the ten weeks [146]. Immunofluorescence staining of the pancreas for CAT and glutathione reductase (GR) revealed an increase in treated animals (co-localized with insulin in the islets of Langerhans) together with an elevation in GPx gene expression.…”

Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury

“…Routes and doses of administrating drugs were chosen based on the preliminary study. 13,14 Basic Protocol Rats were pair-fed and their body weight was monitored daily. After the 4-week treatments, systolic blood pressure was recorded using the tail cuff method (Visitech System, Apex, NC, USA).…”