Melatonin and type 2 diabetes – a possible link?*

Peschke, Elmar; Stumpf, Ina; Bazwinsky, Ivonne; Litvak, Liudmila; Dralle, Henning; Mühlbauer, Eckhard

doi:10.1111/j.1600-079x.2007.00426.x

Cited by 153 publications

(180 citation statements)

References 45 publications

(77 reference statements)

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“…In view of the effects of melatonin on islets and on whole body metabolism, a link between melatonin receptors and type 2 diabetes was suggested [63] following the demonstration of increased levels of MTNR1A and MTNR1B mRNA in pancreatic tissue from patients with type 2 diabetes and increased immunolabelling of MTNR1A and MTNR1B. Although these results were qualitative rather than quantitative, it was postulated that there is a link between the melatonin system and the pathogenesis of the disease.…”

Section: Genome-wide Association Studies and Mtnr1bmentioning

confidence: 99%

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

et al. 2009

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Melatonin is a circulating hormone that is primarily released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms; its levels are high during the night and low during the day. Interestingly, insulin levels also exhibit a nocturnal drop, which has previously been suggested to be controlled, at least in part, by melatonin. This regulation can be explained by the proposed inhibitory action of melatonin on insulin release. Indeed, both melatonin receptor 1A (MTNR1A) and MTNR1B are expressed in pancreatic islets. The role of melatonin in the regulation of glucose homeostasis has been highlighted by three independent publications based on genome-wide association studies of traits connected with type 2 diabetes, such as elevated fasting glucose, and, subsequently, of the disease itself. The studies demonstrate a link between variations in the MTNR1B gene, hyperglycaemia, impaired early phase insulin secretion and beta cell function. The risk genotype predicts the future development of type 2 diabetes. Carriers of the risk genotype exhibit increased expression of MTNR1B in islets. This suggests that these individuals may be more sensitive to the actions of melatonin, leading to impaired insulin secretion. Blocking the inhibition of insulin secretion by melatonin may be a novel therapeutic avenue for type 2 diabetes.

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Section: Genome-wide Association Studies and Mtnr1bmentioning

confidence: 99%

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

et al. 2009

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“…Two distinct G proteincoupled receptors, MTNR1A and MTNR1B, mediate the effects of melatonin. These two receptors have been found to be produced in human pancreatic islets [9,10], and the levels of both are upregulated in type 2 diabetic patients [11]. Furthermore, Lyssenko et al [3] confirmed the presence of MTNR1B in human pancreatic islets and showed increased MTNR1B mRNA expression in carriers of the rs10830963 risk genotype, reporting a negative correlation between MTNR1B mRNA levels and insulin secretion.…”

Section: Introductionmentioning

confidence: 97%

A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals

et al. 2009

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Aims/hypothesis Recently, three groups independently reported that variation in MTNR1B, the gene encoding melatonin receptor 1B, was associated with an increased risk of type 2 diabetes, increased fasting plasma glucose and impaired insulin secretion in populations of European ancestry. In the present study, we investigated whether a single MTNR1B polymorphism was associated with type 2 diabetes in Han Chinese individuals, to elucidate whether this is a cross-populational effect. Methods The MTNR1B variant rs10830963 was genotyped in 1,165 type 2 diabetic patients and 1,105 normoglycaemic control individuals of southern Han Chinese ancestry who were residents of the metropolitan area of Shanghai. The risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex and BMI. A possible association with fasting plasma glucose was analysed in the normoglycaemic control individuals using a multiple linear regression analysis with adjustments for age, sex and BMI. Results The genetic variant rs10830963 was associated with an increased risk of type 2 diabetes in our Han Chinese cohort (OR 1.16, 95% CI 1.03-1.31, p=0.015). As previously described, the risk variant was also associated with increased fasting plasma glucose, showing an increase of 0.068 mmol/l (95% CI 0.036-0.100, p=4×10 −5 ) per risk allele. Conclusions/interpretation A common variant in the MTNR1B gene is associated with an increased risk of type 2 diabetes and increased fasting plasma glucose in Han Chinese, suggesting an important role for this polymorphism in populations of different ethnic and environmental backgrounds.

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“…Human and rodent pancreatic tissues and islets and rodent cell lines has been found to express MT1 and MT2 receptors (10,35,53,55,(61)(62)(63)(64)(65). The occurrence of melatonin receptors in the pancreatic islets proposes that their activation by melatonin might directly influence insulin or glucagon production and provides a biochemical basis to explain how decreased melatonin levels of diabetic patients could affect the function of the pancreas (6,66).…”

Section: Melatonin and Insulin Secretionmentioning

confidence: 99%

“…A low quantity of circulating melatonin occur in patients with type 2 diabetes (11), at the same time upregulated mRNA expression of melatonin membrane receptor was observed (55). Furthermore, polymorphisms in the melatonin receptor gene were linked with fasting blood glucose level and susceptibility to the occurrence of type 2 diabetes (56).…”

Section: Melatonin and Glucose Homeostasismentioning

confidence: 99%

“…insulin levels alters in a reverse fashion to melatonin (94). Decreased melatonin level in irregular manner has been related with diabetes (6,55), which suggests that the melatonin signal is critical for glucose regulation in blood and maintaining homeostasis (95). In patients with type 2 diabetes, gluconeogenesis and endogenous glucose production exhibit circadian rhythm that impel fasting high blood glucose and do not exist in healthy humans (96).…”

Section: Melatonin and Diabetesmentioning

confidence: 99%

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The role of melatonin in diabetes: therapeutic implications

Sharma

Singh

Ahmad

et al. 2015

Arch. Endocrinol. Metab.

110

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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

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Melatonin and type 2 diabetes – a possible link?*

Cited by 153 publications

References 45 publications

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals

The role of melatonin in diabetes: therapeutic implications

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