Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.
Level 3 - non-randomized controlled study
Prospective cohort studies combined with in vitro and human tissue mechanistic analyses
PubMed 19060908 · doi:10.1038/ng.288
What was done
The authors evaluated whether a common genetic risk variant in MTNR1B (melatonin receptor 1B) predicts future type 2 diabetes (T2D) in two prospective cohorts. They assessed early insulin response using oral and intravenous glucose challenges and tracked insulin secretion over time. In laboratory analyses, they measured MTNR1B mRNA and protein localization in human pancreatic islets (from non-diabetic risk carriers and individuals with T2D) and evaluated the effect of melatonin on glucose-stimulated insulin secretion in clonal beta cells.
What was found
The abstract reports no exact numerical values, effect sizes, or p-values. Qualitatively, the risk genotype predicted future T2D across two prospective cohorts, showed impaired early insulin response to both oral and intravenous glucose, and tracked with faster deterioration of insulin secretion over time. MTNR1B mRNA and protein were expressed predominantly in human pancreatic beta cells, with increased receptor expression observed in risk-allele carriers and patients with T2D. Melatonin exposure directly inhibited glucose-stimulated insulin release from clonal beta cells.
Why it matters
This study establishes a functional link between melatonin signaling and pancreatic beta-cell dysfunction, identifying MTNR1B as a direct contributor to impaired insulin secretion and type 2 diabetes risk. It highlights the melatonin receptor pathway as a potential therapeutic target.
Limits
The abstract provides no sample sizes, effect sizes, confidence intervals, or demographic details for the prospective cohorts and human islet donors. In vitro findings in clonal beta cells and isolated islets may not fully capture in vivo human glucose homeostasis or physiological circadian dynamics.
Cited by
- supports Melatonin rises approximately 3 hours before natural bedtime and reduces pancreatic insulin secretion, lowering insulin sensitivity in the evening.