Incretin Effects on b-Cell Function, Replication, andMass The human perspective

There is a progressive deterioration inb-cell function in patients with type2 diabetes. At diagnosis, islet func-tion may be reduced by up to 50 % com-pared with healthy control subjects, and there is also likely to be a reduction in b-cell mass of up to 60%. The reduction in b-cell mass is due to accelerated apo-ptosis. Currently, few pharmacological therapies address this reduction in b-cell mass and function. This means that pa-tients are generally subjected to an in-creasing polypharmacy to control their diabetes, withmost eventually being treated by insulin. Incretin hormones, which are released from the gastrointestinal tract after a meal, enhance glucose-dependent insulin secretion from the pancreas, aid-ing the overall regulation of glucose ho-meostasis in healthy subjects. In addition, these hormones, especially glucagon-like peptide (GLP)-1, have a number of protec-tive effects on theb-cells, including a reduc-tion in apoptosis and enhancement ofb-cell proliferation and neogenesis. These benefits are lost to a significant extent in patients with diabetes. The recently developed di-abetes therapies, GLP-1 receptor agonists, such as exenatide and liraglutide, appear to have beneficial effects on b-cell function and hence offer promise for durable glyce-mic control as well as potentially reducing the micro- and macrovascular complica-tions associated with type 2 diabetes