Abstract | 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 <5.2 mm. The obese subjects were insulin resistant compared to the lean group (homeostasis model of assessment 2 for insulin resistance: obese, 2.6 ± 0.5; lean, 0.8 ± 0.1; P < .001). ISR increased linearly in both cohorts with escalating doses of GLP-1, but the slope of ISR in response to GLP-1 was greater in the obese than in the lean subjects (obese, 0.17 ± 0.03 nmol/min/pm; lean, 0.05 ± 0.01 nmol/min/pm; P < .001). There was a significant association of β-cell GLP-1 sensitivity and insulin resistance (r = 0.83; P < .001), and after correction for homeostasis model of assessment 2 for insulin resistance, the slopes of ISR vs GLP-1 concentration did not differ in the two cohorts (obese, 0.08 ± 0.01; lean, 0.08 ± 0.01; P = .98). However, within the entire study group, β-cell GLP-1 sensitivity corrected for insulin resistance varied nearly 10-fold. CONCLUSIONS:
|
Authors | Benedikt A Aulinger, Torsten P Vahl, Hilary E Wilson-Pérez, Ron L Prigeon, David A D'Alessio |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 100
Issue 6
Pg. 2489-96
(Jun 2015)
ISSN: 1945-7197 [Electronic] United States |
PMID | 25825945
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
|
Chemical References |
- Blood Glucose
- Insulin
- Glucagon-Like Peptide 1
|
Topics |
- Adult
- Blood Glucose
(drug effects, metabolism)
- Drug Resistance
- Female
- Glucagon-Like Peptide 1
(pharmacology)
- Glucose Clamp Technique
- Health
- Humans
- Insulin
(blood, metabolism)
- Insulin Resistance
(physiology)
- Insulin Secretion
- Insulin-Secreting Cells
(drug effects, metabolism)
- Male
- Obesity
(metabolism)
- Thinness
(metabolism)
- Young Adult
|