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

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:

Insulin secretion in response to GLP-1 is proportional to insulin resistance in healthy subjects. However, there is considerable variability in the sensitivity of the β-cell to GLP-1 that is independent of insulin sensitivity.

• 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