Linking MTNR1B Variants to Diabetes: The Role of Circadian Rhythms

Abstract

The melatonin receptor 1B, encoded by the MTNR1B gene, is a member of the melatonin receptor family expressed in many tissues, including pancreatic islets (1). Single nucleotide polymorphisms in MTNR1B have been revealed to be associated with increased blood glucose levels and type 2 diabetes (T2D) incidence according to several genome-wide association studies (GWAS) (2,3), and some of the variants of MTNR1B have been proved to be the proper causal variants in functional studies (4). Additionally, rare loss-of-function variants of MTNR1B were proved to contribute to T2D (5). These association studies in genetics have provided a link between MTNR1B and T2D, but the exact mechanism underlying the association between MTNR1B and T2D risk remains unclear. As a circulating hormone released from the pineal gland, melatonin is an important contributor of seasonal and circadian rhythms (6), and there are complex interplays between melatonin secretion, circadian rhythm, and the circadian master clock of the suprachiasmatic nucleus in the brain (7). The existing literature implies that melatonin plays a role in glucose metabolism (8) and insulin secretion from pancreatic β-cells (9), although the role of melatonin in humans is very complex. According to previous research, impaired glucose metabolism and insulin secretion occurred when the circadian clock was disrupted (10,11), and the quality and quantity of sleep could have affected T2D incidence (12 …