Effect of glucagon-like peptide 1 (7-36 amide) on insulin-mediated glucose uptake in patients with type 1 diabetes

OBJECTIVE - To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type I diabetic patients. RESEARCH DESIGN AND METHODS - We used the hyperinsulinemic-euglycemic clamp (480 pmol . m(-2) . min(-1)) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol . kg(-1) . min(-1). The patients were 41 +/- 3 years old with a BMI of 25 +/- 1 kg/m(2). The mean duration of diabetes was 23 - 3 years. RESULTS - Plasma glucose was allowed to fall from a fasting level of similar to11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were similar to900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 +/- 3 to 150 +/- 17 pmol/l. Plasma glucagon levels fell from the fasting levels of similar to 14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies (similar to40 mumol . kg(-1) . min(-1)). CONCLUSIONS - GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients.