Antidiabetogenic action of truncated glucagon-like peptide-1 in mice

Abstract

Besides its well-known stimulatory action on insulin secretion, glucagon-like peptide-1 (7–36)amide (= GLP-1) has been shown to increase the insulin-independent glucose uptake in normal individuals and the glucose elimination rate during short term conditions in diabetes. Whether such an action is evidented also in rodents and whether it persists after long-term administration are not known. This study therefore examined the influence of the peptide on glucose elimination in insulin deficient diabetic mice both acutely and following long-term administration. GLP-1 was injected intravenously (1 or 32 nmol/kg) together with glucose (2.8 mmol/kg) in both normal and alloxan-diabetic mice. It was found that the peptide at 32 nmol/kg potentiated the glucose elimination rate in both groups, i.e. also under insulin deficient conditions. In normal animals, GLP-1 also potentiated glucose-stimulated insulin secretion. In a second experimental series, GLP-1 was injected subcutaneously at 0.33 or 1.5 nmol twice daily to normal and alloxan-diabetic mice. After 5 days of treatment by the peptide at 1.5 nmol twice daily, the glucose elimination rate was potentiated in both groups, also when the intravenous glucose tolerance test was performed 4 h after the last injection of GLP-1. We therefore conclude that the glucose elimination is enhanced by GLP-1 in both normal and alloxan-diabetic mice, and that this effect persists after a 5 day course of subcutaneous treatment.