Glucagon-like Peptide-1 (GLP-1) is an important incretin hormone which acts as a powerful
insulin secretagogue. Defects in GLP-1 synthesis and secretion are thought to be part of the
pathogenesis of type 2 diabetes. Furthermore GLP-1 based therapy is an important part of the
therapeutic armamentarium for the treatment of type 2 diabetes. The GLP-1 receptor (GLP1R) is
the principal site of action of GLP-1 and GLP-1 receptor agonists like exenatide and
liraglutide. The gene coding for this receptor, GLP1R, is highly polymorphic and contains
numerous non-synonymous Single Nucleotide Polymorphisms (nsSNPs) which could potentially
alter response to endogenous or exogenous GLP-1 or GLP-1R agonists. Indeed there is some in
vitro data to support this concept. We propose to utilize a hyperglycemic clamp to test the
insulin secretory response to infused GLP-1 in healthy volunteers to determine the effect of
genetic variation in GLP1R on response to GLP-1.