Role of GHRH on INS-1E beta-cells: structural proteomic analysis and potential for recovery of endoplasmic reticulum stress

• Grant number: 18/00665-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Karina Rodrigues dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

GHRH is a hormone primarily produced in the hypothalamus, responsible to stimulate the synthesis and secretion of growth hormone. The expression of GHRH and its receptor has been described in peripheral tissues, among them the endocrine pancreas. The actions of GHRH on target cells activate cell survival, proliferation and differentiation pathways. Considering the beta cell mass decline in the progression of type 2 diabetes, such GHRH actions make it a potential target in the beta cell study. One of the mechanisms related to the progressive decline of insular function is endoplasmic reticulum stress (ER). The loss of ER homeostasis activates stress responses, UPR, that occur through exposure to inflammatory cytokines or excess of free fatty acids. As the effects of GHRH have not been fully elucidated in the beta cell, we propose to investigate them by analyzing the structural proteomics in INS-1E beta cells, previously treated with a synthetic GHRH agonist, MR-409. Furthermore, we intend to evaluate the role of GHRH in the modulation of UPR components. For this, INS-1E cells will be treated with a cocktail of inflammatory cytokines for 24h, followed by incubation with MR-409 for 24h. After that, we will evaluate the gene and protein contents of UPR components. To confirm our finding, an ATF6 promoter reporter gene assay will be performed to evaluate its promoter activity. Thus, this project, in its entirety, will contribute to a better understanding of possible effects of GHRH that should impact pancreatic beta cell survival, and may be applied to therapies intended to prevent apoptosis, or reversing the damage caused by inflammation during the progression of type 2 diabetes. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RODRIGUES-DOS-SANTOS, KARINA; SOARES, GABRIELA M.; GUIMARAES, DIMITRIUS S. P. S. F.; ARAUJO, THIAGO R.; VETTORAZZI, JEAN F.; ZANGEROLAMO, LUCAS; MARCONATO-JUNIOR, EMILIO; CAI, RENZHI; SHA, WEI; SCHALLY, V, ANDREW; et al. Effects of growth hormone-releasing hormone agonistic analog MR-409 on insulin-secreting cells under cyclopiazonic acid-induced endoplasmic reticulum stress. Molecular and Cellular Endocrinology, v. 535, SEP 15 2021. (15/12611-0, 18/00665-6, 18/06363-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Karina Rodrigues dos. Role of growth hormone releasing hormone agonist MR-409, on the pancreatic beta cell model INS-1E under endoplasmic reticulum stress. 2020. 56 f. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.