β-Cell Sensitivity to GLP-1 in Healthy Humans Is Variable and Proportional to Insulin Sensitivity

• Published in: The journal of clinical endocrinology and metabolism 2015-06, Vol.100 (6), p.2489-2496
• Main Authors: Aulinger, Benedikt A, Vahl, Torsten P, Wilson-Pérez, Hilary E, Prigeon, Ron L, D'Alessio, David A
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - drug effects; Blood Glucose - metabolism; Drug Resistance; Female; Glucagon-Like Peptide 1 - pharmacology; Glucose Clamp Technique; Health; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance - physiology; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Male; Obesity - metabolism; Original; Thinness - metabolism; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2014-4009

Context: Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance. Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degree to which people vary in their β-cell sensitivity to GLP-1 and the factors contributing to this variability have not been reported. Objective: The objective was to measure the sensitivity of insulin secretion to GLP-1 in cohorts of lean and obese subjects across a broad range of insulin sensitivity. Methods: Insulin secretion was measured during clamped hyperglycemia (7.2 mmol/L) and graded GLP-1 infusion in young, healthy subjects, and GLP-1 sensitivity was computed from the insulin secretion rate (ISR) during progressive increases in plasma GLP-1. Results: All subjects had fasting glucose values