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

Abstract

OBJECTIVE - To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type 1 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/m2. The mean duration of diabetes was 23 ± 3 years. RESULTS - Plasma glucose was allowed to fall from a fasting level of ∼11 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 ∼900 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 ∼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 (∼40 μmol · kg-1 · min-1). CONCLUSIONS - GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients.