Expression and cellular distribution of junctional proteins in pancreatic islets from mice fed a high fat diet for 8 months

• Grant number: 12/13799-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2012
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Carolina Prado de França Carvalho
• Grantee: Camila Calvo de Fontes
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

In a tissue, cells are attached and interact between them through plasma membrane specializations termed cell-cell junctions. These structures are involved in important cell functions such as recognition, communication, adhesion, and cell differentiation. The structure and function of cell junctions may be regulated in vitro and in vivo conditions, and it is remarkable their role in many pathological conditions. The different endocrine cell types found in pancreatic islets are connected by tight junctions, gap junctions, adherens junctions, and desmosomes. Among them, the gap junction (GJ) has been the most studied junction and it is considered to be important for maintaining the adequate functioning of pancreatic beta cells. Many studies revealed that the connexin (Cx) subtype is expressed by the pancreatic beta cells in the Cx36. Recently we demonstrate that the cell coupling mediated by Cx36 channels is crucial for the functional in vivo maturation of rat pancreatic beta cells. However, the role of cell adhesion for insulin secretion and the biochemical characterization of the adherens junction in pancreatic islets is still an open research field. The general aim of this project is to investigate the role of the cell contacts mediated by the gap and adherens junctions and their structural proteins in the dysfunction of pancreatic beta cells during the pathogenesis of type 2 diabetes. To address this issue, C57BL/6 mice will be fed a high fed for a long period of time (8 months). The cellular distribution and expression of some gap- and adherence-associated junctional proteins such as Cx36, E-cadherin, N-cadherin, and N-CAM will be evaluated by immunohistochemistry and Western blot analysis. The pattern of cytoarchitecture (or cell arrangement within the pancreatic islets) will be studied by double-immunostaining reactions for insulin and glucagon detection. The development of this project can add new insights into the possible pathophysiological role of intercellular junctions on pancreatic beta-cell biology.(AU)