The Role of the Cationic Amino Acid Transporter SLC7A2 and Arginine on Pancreatic Alpha Cell Proliferation and Function

Abstract

Inadequate secretion of insulin from pancreatic β-cells in concert with failure to suppress pancreatic α-cell secretion of glucagon results in hyperglycemia and ultimately diabetes. However, the mechanisms for this inappropriate secretory response of α- and β-cells during diabetes has not been fully determined. Although much is known about glucose regulation of islet hormone secretion, how amino acids, such as arginine, have been understudied in hormone secretion and glycemic regulation. Our lab and others have identified a liver-α-cell axis that mediates the regulation of α-cell function through changes in circulating amino acids. Arginine is a potent stimulator of insulin and glucagon secretion, suggest that α-cells and β-cells might have robust arginine transport and sensing capacity. This dissertation aims to elucidate the mechanisms by which arginine stimulates islet hormone secretion and cell proliferation using global and islet cell type specific alterations in expression of the cationic amino acid transporter, SLC7A2, including a surprising role for arginine sensing and α-> β cell communication.