Effect of hypoxia on endoplasmic reticulum stress in insulin-secreting beta cells (INS 1-E).

• Grant number: 22/15809-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Aparecida Emiko Hirata
• Grantee: João Victor de Figueiredo Bani
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is characterized as a metabolic syndrome with multiple origins, which results from a deficiency in the production of insulin and/or its action, and which culminates in hyperglycemia. The pancreatic beta cells are responsible for the production of insulin in the body under proper physiological conditions. However, in diabetic individuals, there is a physiological imbalance that exposes the beta cells to a condition of cellular hypoxia, which in turn appears to involve ER (reticulum stress). The endoplasmic reticulum is an organelle responsible for protein synthesis and secretion. In this context, ER compromises protein synthesis and, since insulin is a protein hormone, aggravates the diabetes picture. As a way to minimize the ER, the endoplasmic reticulum has the UPR (Unfolded Protein Response) system, which aims, then, to reestablish the homeostasis of the ER and restore the function of the organelle, in order to diminish the effects caused by hypoxia, but when this does not occur, apoptotic pathways are activated. The UPR system is formed by 3 sensors PERK1, IRE1 and ATF 6 that, during ER, are activated in order to increase the expression of chaperones and thus facilitate the correct formation of proteins.Given this, the aim of the work is to further evaluate the effects of hypoxia on ER in pancreatic beta cells of the INS1-E strain. Hypoxia will be induced by cobalt chloride and evaluated from the expression of hypoxia-inducing factors (HIF)