Promoting beta-cell function and survival in rodent models of diabetes with an analogue of the incretin hormone, GIP

Diabetes mellitus is a chronic, debilitating disease in which the body is unable to adequately dispose of circulating glucose. As a result, diabetes mellitus causes damage to the eyes, kidneys, peripheral nerves and cardiovascular system. Type 2 diabetes accounts for about 90 percent of diabetes cases and is typically caused by the development of obesity with its associated resistance to the glucose-lowering actions of insulin, compounded by decreased circulating levels of insulin. Insufficient insulin levels in Type 2 diabetes are caused by the diminished function and increased death of the important insulin-secreting beta-cells located in the pancreas. Therefore, therapeutic interventions that improve the function and survival of beta-cells would clearly benefit patients with Type 2 diabetes. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are insulin secreting (incretin) hormones that do just that. As a result, drugs have been developed that enhance the activity of these hormones and they have demonstrated powerful anti-diabetic actions in patients with Type 2 diabetes. Scott Widenmaier’s current research project is building on his earlier work involving the development of a long-acting GIP analogue that has demonstrated potent effects on cultured beta-cells, and triggered acute increases in insulin levels during single dose treatments of diabetic rodents. More recently it has shown potential to decrease fat levels in obese rodents. Mr. Widenmaier’s current project will evaluate the ability of long-term administration of this same GIP analogue to improve the function and survival of beta cells, and decrease circulating glucose levels and obesity in rodent models of Type 2 diabetes. Ultimately, the information resulting from these studies could contribute to a better understanding of the underlying basis for the beneficial effects of incretin therapy, and potentially lead to the development of next generation therapeutics.