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Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy
Open accessAbstract
The past decade has witnessed a revival of interest in the hormone melatonin, partly attributable to the discovery that genetic variation in MTNR1B - the melatonin receptor gene - is a risk factor for impaired fasting glucose and type 2 diabetes (T2D). Despite intensive investigation, there is considerable confusion and seemingly conflicting data on the metabolic effects of melatonin and MTNR1B variation, and disagreement on whether melatonin is metabolically beneficial or deleterious, a crucial issue for melatonin agonist/antagonist drug development and dosing time. We provide a conceptual framework - anchored in the dimension of 'time' - to reconcile paradoxical findings in the literature. We propose that the relative timing between elevated melatonin concentrations and glycemic challenge should be considered to better understand the mechanisms and therapeutic opportunities of melatonin signaling in glycemic health and disease.
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“Notably, the common intronic gain-of-function variant rs10830963 G in MTNR1B shows the strongest association among known single nucleotide polymorphisms with elevated fasting glucose and impaired insulin secretion (6,7)”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant (2026) · cites this paper as [7]
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“There exist conflicting data regarding the effects of melatonin and MTNR1B genotype on glucose control (12)(13)(14) and disagreement on whether melatonin increases or decreases fasting glucose, glucose tolerance, and T2D risk.”
From Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [14]
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“While a few other studies (9–14) have examined the effects of melatonin administration on glycemic control, the mechanisms underlying such association remain unclear (7).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant (2026) · cites this paper as [7]
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“The common melatonin receptor 1B gene (MTNR1B) variant increases risk of type 2 diabetes”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant (2026) · cites this paper as [7]
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Metadata
- Authors
- Garaulet, M., Qian, J., Florez, J. C., Arendt, J., Saxena, R., & Scheer, F. A. J. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Saxena, Richa
- Scheer, Frank A.J.L.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 31
- Issue
- 3
- Pages
- 192-204
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC7349733
- OpenAlex
- W2997273097
- Cited by
- 193
- References
- 94
- Citations by year
- 2026: 28 · 2025: 22 · 2024: 42 · 2023: 32 · 2022: 38 · 2021: 19 · 2020: 12
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- The Spanish Government of Investigation, Development and Innovation (SAF2017-84135-R)
- NIH (R01DK105072, R01DK102696, R01DK107859, R01HL118601, R01DK099512, R01HL140574)
- American Diabetes Association (1-17-PDF-103)
- NIDDK (P30 DK057521, R01 DK105072, K24 DK110550)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- melatonin, glucose metabolism, MTNR1B, melatonin receptors, type 2 diabetes, impaired fasting glucose, genetic variation, melatonin receptor agonists, circadian rhythm, drug dosing
- MeSH terms
- Animals, Blood Glucose, Circadian Rhythm, Diabetes Mellitus, Type 2, Glucose, Humans, Insulin, Melatonin, Genetic Variation, Polymorphism, Single Nucleotide, Receptor, Melatonin, MT2, Carbohydrate Metabolism
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