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 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
SNPs (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
- Aged 18-40
- fasting glucose concentration of less than 95 mg/dl.
- Individuals with a BMI < 19 or > 40 kg/m2
- active systemic illness
- medication that can alter gastric emptying, insulin secretion & action
- history of abdominal surgery (other than appendectomy or tubal ligation).