Melatonin receptors in diabetes: A potential new therapeutical target?

She, Meihua; Laudon, Moshe; Yin, Wang

doi:10.1016/j.ejphar.2014.08.012

Cited by 27 publications

(28 citation statements)

References 42 publications

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“…Melatonin induces GLUT-4 expression in skeletal muscles through an IRS-1 or PI-3 kinase-mediated pathway and enhances glucose transportation [29, 30]. Melatonin binds to MT1 and MT2 receptors on pancreatic β cells, and reduces cAMP and cGMP levels, respectively [17], thereby inhibiting insulin secretion. In diabetic rats, it was also shown that melatonin improves insulin resistance by inhibiting inflammatory cytokine production and oxidative stress and reducing the level of free fatty acids [12, 31].…”

Section: Discussionmentioning

confidence: 99%

“…Ramelteon has a 5.8-fold higher affinity for melatonin MT1 receptor and a 3.4-fold higher affinity for melatonin MT2 receptor compared with melatonin [16]. Although there have been reports on the effect of melatonin on glucose metabolism [12, 17, 18], that of ramelteon has not been discussed. In addition, the efficacy and safety of ramelteon in patients with type 2 diabetes are yet to be researched.…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

et al. 2016

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BackgroundInsomnia is associated with the onset and development of diabetes. Melatonin affects sleep quality and glucose metabolism in diabetic patients with insomnia. We administered ramelteon, an agonist of melatonin, to type 2 diabetic patients and investigated its effects on glucose metabolism and insomnia.MethodsThis multicenter, prospective, randomized, and observational pilot study was performed between April 2014 and April 2015 at three institutes in Japan. Patients were prescribed ramelteon 8 mg/day for 3 months (first period). And patients were divided at random into the continuation group that continued taking ramelteon and the discontinuation group that discontinued taking ramelteon for 3 additional months (second period). The primary endpoint was change in glycated hemoglobin (HbA1c) level. Secondary endpoints were changes in global Pittsburgh sleep questionnaire index (PSQI) score and other glucose metabolism makers.ResultsWe enrolled 42 patients, and 32 patients completed the first period. Their mean HbA1c was 6.7%, and global PSQI score was 8.1 on average. HbA1c level did not change but global PSQI score improved from 8.1 to 7.2 by ramelteon (P = 0.030). Thirty-one patients completed the second period. HbA1c level did not change in the continuation group, but it increased from 6.7% to 6.9% (P = 0.003) in the discontinuation group. Global PSQI score did not change in each group. There was no rebound insomnia.ConclusionTreatment with ramelteon did not change the HbA1c level but improved sleep quality in type 2 diabetic patients with insomnia. Discontinuation of ramelteon slightly increased the HbA1c level and did not worsen sleep quality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

et al. 2016

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“…In humans there are two functional melatonin G protein coupled receptors, MTNR1A (MT 1 ) and MTNR1B (MT 2 ), though a third possible melatonin receptor has been identified [ 74 ]. MT 2 receptors are in various tissues including adipocytes, liver, skeletal muscle and pancreatic β-cells [ 73 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women

et al. 2015

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AimTo identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.MethodFasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.ResultsThere were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000), triglycerides (P = .050), low density lipoprotein (P = .009) and non-fasting blood glucose (15 min) (P = .024) were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC). Non-fasting insulin in South Asians (15–120 min), in South East/East Asians (60–120 min), and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006). The molar ratio of C-peptide AUC/Insulin AUC (P = .045) and adiponectin (P = .037) were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022) and rs10830963 (P = 0.009), which are both near the melatonin receptor MTNR1B.ConclusionsElevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.

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“…So far, several studies already investigated potential roles of MTNR1B in T2DM. But the results of these studies were inconsistent (Hu & Jia, ; She, Laudon, & Yin, ). Therefore, we performed the present meta‐analysis to better evaluate potential associations between MTNR1B genetic variants and T2DM.…”

Section: Introductionmentioning

confidence: 99%

Effects of MTNR1B genetic variants on the risk of type 2 diabetes mellitus: A meta‐analysis

Shen

Yin

2019

Molec Gen & Gen Med

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Background Whether melatonin receptor 1B ( MTNR1B ) variants are associated with type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we performed this meta‐analysis to better explore correlations between MTNR1B variants and T2DM. Methods Literature research was performed in PubMed, Medline, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Totally 21 studies were enrolled to analyses. Pooled overall analyses showed that MTNR1B rs10830963 variant was significantly correlated with the susceptibility to T2DM (allele model: p = 0.02, OR = 0.97, 95% CI 0.95–1.00). Further subgroup analyses by ethnicity of participants revealed that rs10830963 variant was significantly correlated with the susceptibility to T2DM in South Asians, but not in Caucasians or East Asians. No any other positive results were found in overall and subgroup analyses. Conclusions Our findings indicated that MTNR1B rs10830963 variant might serve as a genetic biomarker of T2DM, especially in South Asians.

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Melatonin receptors in diabetes: A potential new therapeutical target?

Cited by 27 publications

References 42 publications

The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women

Effects of MTNR1B genetic variants on the risk of type 2 diabetes mellitus: A meta‐analysis

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