The role of HNF4alfa in expansion of functional pancreatic beta cell in insulin resistant and, STZ-induced diabetic mice.

• Grant number: 13/24670-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2014
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Gustavo Jorge dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hiperglycemia. This disease is due to either absolute (Type 1), or relative (Type 2) insulin deficiency, linked, or not, with insulin resistance (IR). However, during the onset of DM type 2 there is an increase in beta cell mass functionality, induced by IR. This represents an effort to counteract the deleterious effects of IR on metabolism. The HNF4± is a fundamental transcriptional factor to pancreatic ² cells, since it regulates the expression of several proteins, involved in glucose metabolism, and the expression of the insulin gene. The HNF4alfa controls the pregnancy-induced increase in pancreatic beta cells mass, activating ERK-ST5 pathway. It is known that HNF4± regulates the expression of ERK, that controls the transcriptional factor NeuroD expression, and the activation of PDX-1, essentials for pancreatic islet cdevelopment and survival. In this project we will evaluate the role of HNF4alfa on RI-induced increase in pancreatic beta cell mass, as well as, it role in pancreatic beta cell regeneration in STZ-induced diabetes mice.