The role of melatonin in diabetes: therapeutic implications

Abstract

Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca 2+ from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes. Arch Endocrinol Metab.2015;59(5):391-9

Chronomedicine and type 2 diabetes: shining some light on melatonin

“…In addition to this dichotomy, we find that melatonin can have conflicting impacts on target tissues, such as the pancreatic beta cell, in both rodents and humans [49,111,140], and highly variable effects on systemic glucose homeostasis and insulin sensitivity [28,29,111,141,142]. In vitro, melatonin inhibits insulin secretion by lowering cAMP and cGMP production [27,49,[143][144][145]. This effect is logical in humans, presuming that melatonin acts to suppress insulin during the night, effectively sensitising the beta cell in preparation for breakfast, but is more difficult to rectify in night-time eating rodents.…”

“…The pros and cons of melatonin therapy for glycaemic control in humans With regard to treatment of type 2 diabetes with melatonin, the number of controlled clinical trials is somewhat limited, and the results are often mixed, with both positive and negative effects on glycaemic control being reported [27,145,151,152]. Evidence from animal and human studies indicates that melatonin or synthetic melatonin receptor agonists can alter glucose homeostasis [5,145,153].…”

“…Evidence from animal and human studies indicates that melatonin or synthetic melatonin receptor agonists can alter glucose homeostasis [5,145,153]. The study of isolated human islets from both healthy and type 2 diabetic donors has revealed that melatonin can normalise glucose-stimulated insulin secretion following exposure to hyperglycaemia [115].…”

Melatonin: A Silent Regulator of the Glucose Homeostasis

“…Molecular and immunocytochemical studies confirmed the presence of melatonin receptors MT1 and MT2 in the islets of Langerhans and also in human pancreatic tissue [13]. MT1 and/ or MT2-mediated melatonin action decreases glucose-stimulated insulin secretion in isolated rat pancreatic islets and rat insulinoma beta-cells.…”

The role of melatonin in development of gestational diabetes mellitus

“…Показано, что у беременных с ГСД снижены связывающая способность рецептора ГЛЮТ4 и транспорт глюкозы в жировую ткань и скелетные мышцы [71,75,76]. Применение мелатонина и стабилизация циркадного рит-ма нормализуют метаболизм, оптимизиру-ют течение беременности и развитие плода [28,49,77]. Таким образом, результаты эксперимен-тальных и клинических исследований, рас-ширившие наше представление о механизмах регуляции углеводного обмена и энергети-ческого метаболизма, указывают на возмож-ность прогнозирования осложнения будущей беременности сахарным диабетом еще на этапе планирования семьи и своевременного прове-дения профилактических мероприятий, вклю-чающих прежде всего нормализацию суточного ритма сна и бодрствования, энергетического метаболизма, антиоксидантного статуса и при необходимости терапию с использованием ме-латонина.…”