Work

The Glucagonostatic and Insulinotropic Effects of Glucagon-Like Peptide 1 Contribute Equally to Its Glucose-Lowering Action

Year: 2010

Type: article

Abstract: OBJECTIVE: Glucagon-like peptide 1 (GLP-1) exerts beneficial antidiabetic actions via effects on pancreatic beta- and alpha-cells. Previous studies have focused on the improvements in beta-cell function, while the inhibition of alpha-cell secretion has received less attention. The aim of this research was to quantify the glucagonostatic contribution to the glucose-lowering effect of GLP-1 infusions in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Ten male patients with well-regulated type 2 diabetes (A1C 6.9 +/- 0.8%, age 56 +/- 10 years, BMI 31 +/- 3 kg/m(2) [means +/- SD]) were subjected to five 120-min glucose clamps at fasting plasma glucose (FPG) levels. On day 1, GLP-1 was infused to stimulate endogenous insulin release and suppress endogenous glucagon. On days 2-5, pancreatic endocrine clamps were performed using somatostatin infusions of somatostatin and/or selective replacement of insulin and glucagon; day 2, GLP-1 plus basal insulin and glucagon (no glucagon suppression or insulin stimulation); day 3, basal insulin only (glucagon deficiency); day 4, basal glucagon and stimulated insulin; and day 5, stimulated insulin. The basal plasma glucagon levels were chosen to simulate portal glucagon levels. RESULTS: Peptide infusions produced the desired hormone levels. The amount of glucose required to clamp FPG was 24.5 +/- 4.1 (day 1), 0.3 +/- 0.2 (day 2), 10.6 +/- 1.1 (day 3), 11.5 +/- 2.7 (day 4), and 24.5 +/- 2.6 g (day 5) (day 2 was lower than days 3 and 4, which were both similar and lower than days 1 and 5). CONCLUSIONS: We concluded that insulin stimulation (day 4) and glucagon inhibition (day 3) contribute equally to the effect of GLP-1 on glucose turnover in patients with type 2 diabetes, and these changes explain the glucose-lowering effect of GLP-1 (day 5 vs. day 1).

Source: Diabetes

DOI: 10.2337/db09-1414

Authors: Kristine J. Hare, Tina Vilsbøll, Meena Asmar, Carolyn F. Deacon, Filip K. Knop, Jens J. Holst

Institutions: University of Copenhagen, Glostrup Hospital, Gentofte Hospital

Language: English

Topic: Diabetes Treatment and Management

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: American Diabetes Association