Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With...

Area of Science:

• Endocrinology
• Metabolic Health
• Genetics

Background:

• Melatonin use has surged, coinciding with a rise in type 2 diabetes.
• A common variant in the melatonin receptor 1B gene (MTNR1B) is linked to increased type 2 diabetes risk.
• Concerns exist regarding melatonin's potential adverse metabolic effects, necessitating genotype-specific research.

Purpose of the Study:

• To investigate melatonin's effects on glucose homeostasis.
• To assess melatonin's impact on beta-cell function (first- and second-phase responsivity).
• To determine if MTNR1B risk allele carriers experience amplified adverse metabolic effects from melatonin.

Main Methods:

• A randomized, double-blind, placebo-controlled, crossover trial involving 21 healthy adults (10 MTNR1B risk carriers, 11 noncarriers).
• Participants received 5 mg oral melatonin or placebo over 5-day laboratory protocols.
• Glycemic dynamics were analyzed using insulin-modified intravenous glucose tolerance tests and minimal-model analysis.

Main Results:

• Melatonin impaired glucose tolerance and reduced early C-peptide responses in MTNR1B risk carriers, but not noncarriers.
• In carriers, melatonin suppressed glucose-stimulated first-phase beta-cell responsivity by 40% and slowed insulin-induced second-phase insulin secretion.
• Melatonin prevented exogenous insulin-induced hypoglycemia in carriers, unlike in noncarriers.

Conclusions:

• Blunted beta-cell responsiveness to glucose is a key mechanism linking melatonin to diabetes risk.
• Dysregulated insulin negative feedback by melatonin contributes to increased diabetes risk in carriers.
• Findings support a genotype-based personalized approach to melatonin use for metabolic health.