Molecular Mechanisms of the Melatonin Receptor Pathway Linking Circadian Rhythm to Type 2 Diabetes Mellitus

Night-shift work and sleep disorders are associated with type 2 diabetes (T2DM), and circadian rhythm disruption is intrinsically involved. Studies have identified several signaling pathways that separately link two melatonin receptors (MT(1) and MT(2)) to insulin secretion and T2DM occurrence, but a comprehensive explanation of the molecular mechanism to elucidate the association between these receptors to T2DM, reasonably and precisely, has been lacking. This review thoroughly explicates the signaling system, which consists of four important pathways, linking melatonin receptors MT(1) or MT(2) to insulin secretion. Then, the association of the circadian rhythm with MTNR1B transcription is extensively expounded. Finally, a concrete molecular and evolutionary mechanism underlying the macroscopic association between the circadian rhythm and T2DM is established. This review provides new insights into the pathology, treatment, and prevention of T2DM.