Involvement of prolactin in the prevention of beta cells dysfunction and death induced by endoplasmic reticulum stress

• Grant number: 11/22852-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2012
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Tarlliza Romanna Nardelli
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 13/25835-8 - Identification of novel IRE-1alpha interacting proteins and their role in pancreatic beta cells ER stress and inflammation, BE.EP.DD

Abstract

The two most important forms of Diabetes are known as type 1 (DM1) and 2 (DM2). This disease affects millions of people worldwide, lowering their quality and life expectancy. The functional reduction and increased beta cell apoptosis is a key feature in both DM1 and DM2, and in both cases, the therapies currently used are not able to prevent this beta cell loss. Increasing evidences has shown that activation of Endoplasmic Reticulum (ER) stress in beta cell in response to proinflammatory cytokines (DM1) or chronic exposure to saturated fatty acids (DM2) is crucial for induction of beta cell dysfunction and death. Results from our group showed that pregnancy improves the handling of Ca2+, increases the expression of Ca2+ channel voltage depedente (CaV±1.2) and insulin secretion in islets isolated from obese rats by cafeteria diet. A candidate for these improvements is the hormone Prolactin (PRL), as this hormone is one of those responsible for several beneficial changes observed in pancreatic beta cells during pregnancy. On the other hand, we observed that the treatment of beta cells with proinflammatory cytokines inhibit the expression of PRL receptor (PRLr), which is linked to decreased recovery capacity of these cells after an autoimmune attack. Therefore, the proposed study aims a better understanding of the effect of PRL in regulating the homeostasis of Ca2+ as well as the possible preventive effect that this hormone may exert on the development of the ER stress, particularly in insulin-secreting cells during obesity and/or an autoimmune attack. Despite the existing knowledge about the action of the PRL during pregnancy, the discovery of a new beneficial role and protective effect on beta cell function as well as preserving its viability could show the way for the prevention/treatment both in DM1 and in DM2 through the modulation of specific signaling pathways of PRL. (AU)

Academic Publications

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

NARDELLI, Tarlliza Romanna. Envolvimento da prolactina na prevenção da disfunção e morte de células beta pancreáticas induzidas por citocinas pró-inflamatórias. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.