Melatonin, endocrine pancreas and diabetes
1Institute of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Germany. elmar.Peschke@medizin.uni-halle.de
Abstract:
Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release. [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'.] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way, melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin. (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm. This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion. (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves. (v) Melatonin influences diabetes and associated metabolic disturbances. The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS. Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. Results suggest that melatonin in pharmacological doses provides protection against ROS. (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin.
Insights
Melatonin, a hormone, regulates insulin secretion and exhibits protective effects against diabetes-related oxidative stress. It influences circadian rhythms in pancreatic islets and shows altered levels in diabetic conditions, highlighting its role in metabolic health.
Area of Science:
- Endocrinology
- Chronobiology
- Molecular Biology
Background:
- Melatonin is a key hormone involved in regulating physiological processes, including metabolic functions.
- Insulin secretion and pancreatic beta-cell function are crucial for glucose homeostasis.
- Disruptions in melatonin signaling and oxidative stress are implicated in diabetes pathogenesis.
Purpose of the Study:
- To elucidate the mechanisms by which melatonin influences insulin secretion via specific receptor pathways.
- To investigate the role of melatonin in the circadian regulation of insulin release from pancreatic islets.
- To assess the protective effects of melatonin against oxidative stress in beta-cells and its implications in diabetes.
Main Methods:
- Investigated melatonin's effects on insulin secretion in vivo and in vitro, focusing on MT(1)/MT(2) receptor-mediated pathways (cAMP, cGMP, IP3).
- Analyzed the circadian rhythm of insulin secretion and the influence of melatonin on this rhythm in isolated islets.
- Examined the impact of diabetogens (alloxan, streptozotocin) on beta-cells and melatonin's protective role against reactive oxygen species (ROS).
- Compared plasma melatonin levels and arylalkylamine-N-acetyltransferase (AANAT) activity in diabetic and non-diabetic subjects.
Main Results:
- Melatonin, acting through MT(1)/MT(2) receptors and G(i)-proteins, inhibits cAMP and cGMP pathways, decreasing insulin release, while potentially increasing it via the IP(3) pathway.
- Insulin secretion exhibits a circadian rhythm influenced by melatonin, which induces phase shifts.
- Melatonin demonstrates protective effects against ROS-induced damage to beta-cells, suggesting a therapeutic potential in diabetes.
- Diabetic rats and humans show lower plasma melatonin levels and AANAT activity, alongside increased pineal AANAT mRNA and decreased insulin receptor mRNA.
Conclusions:
- Melatonin significantly modulates insulin secretion through complex receptor-mediated signaling pathways.
- Melatonin plays a critical role in the circadian regulation of pancreatic islet function and insulin release.
- Pharmacological doses of melatonin may offer protection against diabetes-associated oxidative stress.
- Alterations in melatonin metabolism and signaling are closely linked to insulin resistance and diabetes.
Related Concept Videos
01:29The Endocrine System
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are co-secreted in...
01:16Cells and Secretions of the Pancreas
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
01:16Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
01:27Major Hormones and Their Functions
Oxytocin, produced in the hypothalamus and released by the pituitary gland, plays a role in social bonding, childbirth, and lactation.
01:26Diabetes Mellitus: Introduction