Electronic Thesis and Dissertation Repository

Collagen IV-β1Integrin Regulation of Exocytotic Machinery in Pancreatic Beta-Cell Insulin Secretion

Malina Barillaro, The University of Western Ontario

Abstract

Diabetes is a prevalent metabolic disease characterized by impaired insulin secretion, action, or both. β1-integrin is a key receptor that regulates cell-ECM interactions and is important in maintaining beta-cell functions, including insulin secretion. However, little is reported about the relationship between β1-integrin and the exocytotic proteins involved in insulin secretion. This study examined the influence of ECM-mediated β1-integrin activation on exocytotic machinery involved in insulin secretion using rat insulinoma (INS-1) cells. Collagen IV (COL IV) promoted INS-1 cell adhesion, spreading, and insulin secretion. Additionally, these cells displayed changes in levels and localization of exocytotic proteins involved in insulin secretion. β1-integrin antibody blocking on cells cultured on COL IV showed significantly reduced adhesion, spreading, and insulin secretion along with reduced exocytotic protein levels. Additionally, b1-integrin blocking influenced the localization of exocytotic proteins at varied time points of glucose stimulation. These results indicate that specific ECM-integrin interactions are critical for proper beta-cell function.