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J Endocrinol. 2014 Feb 10;220(3):291-304. doi: 10.1530/JOE-13-0426. Print 2014 Mar.

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

Author information

1
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.

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 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.

KEYWORDS:

diabetes; gene expression; immunohistochemistry; insulin; islet cells

PMID:
24353307
DOI:
10.1530/JOE-13-0426
[Indexed for MEDLINE]
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