In vivo effect of reduced expression of ARHGAP21 on glucose homeostasis and expression of key proteins of glucose metabolism in pancreatic islet and peripheral tissues

• Grant number: 14/03547-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2014
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Fernanda Raimondi da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 12/14993-9 - Type 3 muscarinic receptor activation and association with ADP-rybosilation factor 1 and 6 on the pancreatic beta-cell function: downstream signalling pathways, islet arquitecture and insulin secretion, AP.JP

Abstract

The presence of ARF 1 and 6 in epithelial cells is essential in the process of coordinating the turnover adherens junctions, through the spatial distribution and traffic of the components of the complex formed by adhesion molecules, regulating cellular morphological changes (Palacios et al, 2001; Watanabe et al, 2009; Hiroi, 2009). In ² cell, small GTPases as ARFs play a key role in insulin secretion (Kowluru, 2010). Thus, these GTPases might also be relevant in for efficient adhesion between adjacent cells in the pancreatic islet. In fact, adhesion molecules, such as epithelial adherens junctions cadherin (ECAD), play essential role in pancreatic islet architecture (Rogers et al, 2007; Hodgkin et al, 2007; Brereton et al, 2006). There is evidence that the immuno-neutralization of ECAD in pseudoislets constructed from MIN6 ² cell present impaired oscillation of cytoplasmic Ca2+ and insulin secretion in response to glucose, suggesting that functional adherens junctions play essential role on the function of cell-². Thus, considering that ARHGAP21 activates GTPase function in ARFs, and also the involvement of ARFs in pathways that coordinate the turnover of adherens junctions, this project aims to investigate the role of ARHGAP21 on the expression of ECAD in islets, the ² cell area as well as the control of insulin secretion in isolated islets in animals with reduced expression of ARHGAP21 and treated with high fat diet.