The effects of exendin-4 on glucose homeostasis, pancreatic and duodenal homebox 1, and glucose transporter 2 gene expression disturbance induced by bisphenol A in male mice. The effects of exendin-4 on pancreatic gene expression

Akram Ahangarpour; Golshan Afshari; Seyyed Ali Mard; Ali Khodadadi; Mahmoud Hashemitabar

Akram Ahangarpour 1. Department of Physiology, Health Research Institute, Diabetes Research Center, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz; Iran
Golshan Afshari 2. Clinical Research Development Unit of Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Seyyed Ali Mard 3. Physiology Research Center, Research Institute for Infectious Diseases of Digestive System and Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Ali Khodadadi 4. Cellular and Molecular Research Center, Department of Immunology science, Ahvaz Jundishapur University of Medical Sciences, Faculty of Medicine, Ahvaz, Iran
Mahmoud Hashemitabar 5. Cellular and Molecular Research Center, Department of Anatomical Science, Ahvaz Jundishapur University of Medical Sciences, Faculty of Medicine, Ahvaz, Iran.

Keywords: Bisphenol A, exendin-4, GLUT2, Pdx1

Abstract

Introduction: Bisphenol A (BPA) is a substance used in the packaging of food and beverages. It can bind to estrogen receptors with destructive consequences. Exendin-4 is a 39-amino acid peptide that bonds with GLP-1 receptors and stimulates insulin secretion. In this study, we aimed to explore the effect of exendin-4 on resolving BPA side effects. Materials and method: We tested the effects of five concentrations of exendin-4 alone in combination with BPA on insulin secretion from isolated islets in in-vitro assay. Following in-vivo part of an examination, both BPA and exendin-4 were prescribed alone. Then, in combination for 20 days, next blood glucose, plasma insulin level, and Pdx1 and GLUT2 gene expression were examined. Result: Studies showed that BPA increased the blood glucose level, whereas exendin-4 was useful in removing these symptoms. Quantitative real-time polymerase chain reaction results (PCR) showed that BPA decreased the expression level of Pdx1 and GLUT2 genes in pancreatic tissue, whereas exendin-4 had a preventive role. In an in-vitro experiment, BPA increased the percentage of apoptotic cells, whereas exendin-4 restrained it. Conclusion: We observed evidence, such as a decrease in apoptosis in pancreatic islet cells and increase in Pdx1 and GLUT2 gene expression in the pancreas tissue. This can be an indication of the protective and supportive effects of exendin-4 on the pancreatic tissue, as well as the prevention of hyperglycemia in this assay.