Incretin Effects on β-Cell Function, Replication, and Mass

There is a progressive deterioration in b-cell function in patients with type 2 diabetes. At diagnosis, islet function may be reduced by up to 50% compared 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 apoptosis. Currently, few pharmacological therapies address this reduction in b-cell mass and function. This means that patients are generally subjected to an increasing 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, aiding the overall regulation of glucose homeostasis in healthy subjects. In addition, these hormones, especially glucagon-like peptide (GLP)-1, have a number of protective effects on theb-cells, including a reduction in apoptosis and enhancement ofb-cell proliferation and neogenesis. These benefits are lost to a significant extent in patients with diabetes. The recently developed diabetes 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 glycemic control as well as potentially reducing the microand macrovascular complications associated with type 2 diabetes.