GLP1R Polymorphisms and Response to GLP1
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion|
- Insulin Secretion at 150-180 Minutes. [ Time Frame: 150 - 180 minutes after GLP-1 infusion ] [ Designated as safety issue: No ]The 180 minute value represents the mean of the values obtained at 150, 160, 170, and 180 minutes.
- Insulin Secretion at 210-240 Minutes [ Time Frame: 210 - 240 minutes after GLP-1 infusion ] [ Designated as safety issue: No ]The 240 minute value represents the mean of values obtained at 210, 220, 230, and 240 minutes.
|Study Start Date:||November 2007|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
All participants recieved GLP-1 intravenously at 0.75 pmol/kg/min for the first hour and then at 1.5 pmol/kg/min for the next hour
GLP-1 infused at 0.75 pmol/kg/min from 121-180 minutes, GLP-1 infused at 1.55 pmol/kg/min from 181-240 minutes,