Role of growth hormone releasing hormone agonist MR-409, on the pancreatic beta cell model INS-1E under endoplasmic reticulum stress

Author(s)

Karina Rodrigues dos Santos

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2020-02-28

Examining board members

Claudio Chrysostomo Werneck; Camila Aparecida Machado De Oliveira

• Advisor: Helena Cristina de Lima Barbosa Sampaio

Abstract

The growth-hormone-releasing hormone (GHRH) is a hormone produced in the hypothalamus, responsible for inducing the synthesis and secretion of growth hormone by the pituitary. However, recently, its action has also been demonstrated in peripheral tissues, among them the endocrine pancreas. In target cells, GHRH elicits signaling pathways that culminate in increased cell survival, proliferation and differentiation. Thus, considering the decline in beta cell mass concomitant with the progression of type 2 diabetes mellitus (DM2), GHRH becomes a potential therapeutic agent. However, its mechanisms of action are not entirely understood. The endoplasmic reticulum (ER) stress is one of the mechanisms related to the progressive decline of islet function, contributing to the progress of DM2. As the effects of GHRH and its agonists have not been fully elucidated in the beta cell, we propose to investigate them by evaluating the role of the GHRH agonist, MR-409, in cells under ER stress. The results show that the agonist was not able to prevent cells of ER stress. Despite this, cells under ER stress and treated with the agonist survive longer than those without the treatment. This survival may be due, in part, to an increase in anti-apoptotic Bcl-2 family proteins and prevention to oxidative stress. These responses may be due to the greater phosphorylation of the cAMP response element-binding protein (CREB) triggered by the MR-409 signaling pathway. Our data indicate the effect of MR-409 in partially attenuating apoptosis in an insulin-secreting cell line under ER stress (AU)

• FAPESP's process: 18/00665-6 - Role of GHRH on INS-1E beta-cells: structural proteomic analysis and potential for recovery of endoplasmic reticulum stress
• Grantee: Karina Rodrigues dos Santos
• Support Opportunities: Scholarships in Brazil - Master