New evidence for a role of melatonin in glucose regulation

Glucose triggers insulin secretion of the pancreatic β-cells. The pineal hormone melatonin interferes in this process by inhibiting secretion and transmitting circadian timing information to the islets. Circadian insulin secretion is adapted to day/night changes through melatonin-dependent synchronization. In rats and mice, melatonin levels are high during the dark period, which is their active feeding period, while, in humans, melatonin levels are high during the overnight fasting and sleeping period. This implies a different read-out of melatonin signaling in day-active species, including man. Dysregulation of circadian secretion may be a key to the increase of type 2 diabetes (T2D). This review discusses the impact of melatonin on insulin secretion transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 (MTNR1a) and MT2 (MTNR1b) and the second messengers cAMP, cGMP and IP3. This is an important topic since, in several genetic association studies, single nucleotide polymorphisms of the human MT2-receptor have been described as being causally linked with an elevated risk of developing T2D. This article summarizes interrelationships between melatonin and insulin in type 1 diabetic (T1D) and type 2 diabetic (T2D) rats and humans.