Drug development for the treatment of type 2 diabetes mellitus.
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Our laboratory is performing studies of the "Incretin Mimetics", a newly recognized class of blood glucose-lowering agents that stimulate pancreatic insulin secretion, and which are likely to be the next line of defense for the treatment of type 2 diabetes mellitus. Incretin mimetics mimic the action of GLP-1 (glucagon-like peptide-1), a naturally-occurring incretin hormone secreted by L-cells of the intestine, and which when administered to type 2 diabetic subjects, lowers concentrations of blood glucose.
Why are GLP-1 and the incretin mimetics of special interest? Perhaps most remarkable is the finding that the immediate blood glucose-lowering action of these compounds in type 2 diabetic subjects is self-terminating once normoglycemia is achieved. Thus, unlike administered insulin, there exists a natural safeguard such that these agents are less likely to produce hypoglycemia when they are adminstered for therapeutic purposes. One such incretin mimetic is Amylin Pharmaceutical's Byetta. It is an insulin secretagogue that is structurally-related to GLP-1, but unlike GLP-1 it exhibits an extended duration of action. Understanding how the beneficial "antidiabetogenic" actions of GLP-1 and Byetta are achieved is a primary focus of my research.