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

Mohamed Lotfy, Jaipaul Singh, Hameed Rashed, Saeed Tariq, Erika Zilahi, Ernest Adeghate

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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 groupwere treated with exenatide (1 μg/kg bodyweight (BW)) for 10weeks. Blood plasmawas taken for biochemical analyseswhile 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 BWgain 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.

Original languageEnglish
Pages (from-to)291-304
Number of pages14
JournalJournal of Endocrinology
Volume220
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Diabetes
  • Gene expression
  • Immunohistochemistry
  • Insulin
  • Islet cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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