Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes.
Level 3 - non-randomized controlled study
Non-randomized human genotype-stratified challenge study paired with preclinical and animal mechanistic experiments
PubMed 27185156 · doi:10.1016/j.cmet.2016.04.009
What was done
The authors investigated the functional consequences of a type 2 diabetes (T2D) risk G-allele in the melatonin receptor 1b (MTNR1B) gene. They assessed MTNR1B expression in human pancreatic islets by genotype, evaluated cAMP signaling and insulin secretion in MTNR1B-overexpressing insulin-secreting cells, examined insulin secretion in melatonin receptor-deficient mice, and conducted a human recall-by-genotype physiological study evaluating insulin and glucose responses to melatonin administration.
What was found
Islets from risk G-allele carriers exhibited increased MTNR1B expression. In cellular models, melatonin decreased cAMP levels, and MTNR1B overexpression augmented melatonin's suppression of insulin release. Receptor-knockout mice displayed increased insulin secretion. In humans, acute melatonin administration decreased insulin secretion and elevated blood glucose levels to a greater extent in G-allele carriers than non-carriers. Specific numerical values, effect sizes, and p-values were not reported in the abstract.
Why it matters
This work provides a mechanistic explanation for how genetic variation in MTNR1B contributes to type 2 diabetes risk by demonstrating that enhanced melatonin signaling impairs beta-cell insulin secretion. It also indicates that melatonin plays a physiological role in suppressing nocturnal insulin release.
Limits
The abstract does not disclose sample sizes, participant demographics, dosage regimens, or quantitative outcome statistics for the human, animal, or cellular experiments. The long-term clinical effects of exogenous melatonin or receptor antagonism on diabetes development were not assessed.
Cited by
- supports Melatonin rises approximately 3 hours before natural bedtime and reduces pancreatic insulin secretion, lowering insulin sensitivity in the evening.