Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans

• Published in: Diabetes care Vol. 26; no. 10; pp. 2860 - 2864
• Main Authors: AHREN, Bo, HOLST, Jens J, MARI, Andrea
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2003
• Subjects: Aged; Biological and medical sciences; Blood Glucose; C-Peptide - blood; Care and treatment; Clinical Medicine; Diabetes. Impaired glucose tolerance; Eating; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucagon; Glucagon - administration & dosage; Glucagon - blood; Glucagon-Like Peptide 1; Hormones. Endocrine system; Humans; Ingestion; Insulin - blood; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Klinisk medicin; Measurement; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Peptide Fragments - administration & dosage; Peptide Fragments - blood; Pharmacology. Drug treatments; Physiological aspects; Postprandial Period; Protein Precursors - administration & dosage; Protein Precursors - blood; Type 2 diabetes; Denmark; Italy; Sweden; Human; Pancreatic hormone; Healthy subject; Postprandial; Treatment efficiency; Insulin; Glucagon like peptide 1; Dose activity relation; Endocrine secretion; Protein hormone; Treatment; Female; Hormone replacement therapy; Glycemia
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/diacare.26.10.2860

Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans Bo Ahrén , MD, PHD 1 , Jens J. Holst , MD, PHD 2 and Andrea Mari , PHD 3 1 Department of Medicine, Lund University, Lund, Sweden 2 Department of Medical Physiology, the Panum Institute, Copenhagen University, Copenhagen, Denmark 3 Institute of Biomedical Engineering, National Research Council, Padua, Italy Address correspondence and reprint requests to Dr. Bo Ahrén, Department of Medicine, B11 BMC, SE-221 84 Lund, Sweden. E-mail: bo.ahren{at}med.lu.se Abstract OBJECTIVE —Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS —Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m 2 ) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg –1 · min –1 ), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS —GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m 2 with GLP-1 versus 21.0 ± 1.6 nmol/m 2 with saline ( P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min −1 · m 2 · mmol −1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration ( r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI. CONCLUSIONS —Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion. GLP-1, glucagon-like peptide 1 Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted June 24, 2003. Received May 17, 2003. DIABETES CARE