Apoptosis in Pancreatic b-Cells in Type 1 and Type 2 Diabetes 31

Apoptosis plays an important role in the pathophysiology of both type 1 and type 2 diabetes. In type 1 diabetes, β-cell death by apoptosis following autoimmune insulitis causes an absolute insulin deficiency triggered by an extrinsic receptormediated pathway, which activates a cascade of caspase family reaction. The etiology of type 2 diabetes is multifactorial, including obesity-associated insulin resistance, defective insulin secretion, and loss of β-cell mass through β-cell apoptosis. β-cell apoptosis is mediated through a milliard of caspase family cascade machinery in both type 1 and type 2 diabetes. The glucose-induced insulin secretion is the principle pathophysiology of diabetes and insufficient insulin secretion results in chronic hyperglycemia and diabetes. Recently, hyperglycemia-induced β-cell apoptosis has been extensively studied with regard to the balance of pro-apoptotic genes (Bad, Bid, and Bik) and the antiapoptotic Bcl family toward apoptosis in in vitro isolated islets. Apoptosis can only occur when the concentration of pro-apoptotic Bcl-2 exceeds that of antiapoptotic proteins at the mitochondrial membrane of the intrinsic pathway.