Increased melatonin signaling is a risk factor for type 2 diabetes
Open accessAbstract
Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The MTNR1B risk variant rs10830963 confers increased expression of the melatonin receptor in human pancreatic islets.
“The MTNR1B risk variant rs10830963 has a strong association with fasting glucose and confers increased expression of the melatonin receptor in human pancreatic islets (11).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
The melatonin receptor is a G-protein-coupled receptor that mainly acts by interfering with cAMP formation through inhibitory G proteins, inhibiting adenylate cyclase and subsequently inhibiting insulin release.
“This melatonin receptor is a G-protein-coupled receptor that mainly acts via interfering with the formation of cAMP through inhibitory G proteins, inhibiting adenylate cyclase and subsequently inhibiting insulin release (11).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
The MTNR1B risk variant rs10830963 has a strong association with fasting glucose.
“The MTNR1B risk variant rs10830963 has a strong association with fasting glucose and confers increased expression of the melatonin receptor in human pancreatic islets (11).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
The impairment of glucose tolerance and decrease in insulin secretion during late dinner timing might be partly due to the 3.5-fold higher melatonin concentrations.
“This difference might be partly due to the 3.5-fold higher melatonin concentrations, as supported by our earlier trial in which acute melatonin administration impaired glucose tolerance and in vitro b-cell experiments showing decreased insulin secretion due to melatonin (10,11,18,28).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
MTNR1B overexpression augmented the inhibition of insulin release exerted by melatonin.
“results shown in insulin-secreting cells (11) that demonstrated that MTNR1B overexpression augmented the inhibition of insulin release exerted by melatonin.”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
Melatonin contributes to impaired glucose homeostasis by inhibiting insulin secretion.
“Thus, our study supports the hypothesis that melatonin contributes to impaired glucose homeostasis by inhibiting insulin secretion”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
Previous studies have shown that the association with fasting glucose during the day (typically morning) is robust and reproducible.
“Furthermore, while previous studies have shown that the association with fasting glucose during the day (typically morning) is robust and reproducible (11)”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [11]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Global estimates of the prevalence of diabetes for 2010 and 2030
Shaw, J. E., Sicree, R. A., & Zimmet, P. Z. (2010) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2009.10.007 · Cited by 7,216 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351 · see citing works
Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes
Marcheva, B., Ramsey, K. M., Buhr, E. D., Kobayashi, Y., Su, H., Ko, C. H., Ivanova, G., Omura, C., Mo, S., Vitaterna, M. H., et al. (2010) · Nature · doi:10.1038/nature09253 · Cited by 1,525 · see citing works
Clinical risk factors, DNA variants, and the development of type 2 diabetes
Lyssenko, V., Jonsson, A., Almgren, P., Pulizzi, N., Isomaa, B., Tuomi, T., Berglund, G., Altshuler, D., Nilsson, P., & Groop, L. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801869 · Cited by 938 · see citing works
Self-citationHohmeier, H. E., Mulder, H., Chen, G., Henkel-Rieger, R., Prentki, M., & Newgard, C. B. (2000) · Diabetes · doi:10.2337/diabetes.49.3.424 · Cited by 922 · see citing works
Variants in MTNR1B influence fasting glucose levels
Prokopenko, I., Langenberg, C., Florez, J. C., Saxena, R., Soranzo, N., Þorleifsson, G., Loos, R. J. F., Manning, A. K., Jackson, A., Aulchenko, Y. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.290 · Cited by 743 · see citing works
Lyssenko, V., Nagorny, C. L. F., Erdos, M. R., Wierup, N., Jonsson, A., Spégel, P., Bugliani, M., Saxena, R., Fex, M., Pulizzi, N., et al. (2009) · Nature Genetics · doi:10.1038/ng.288 · Cited by 742 · see citing works
Prevention of fat-induced insulin resistance by salicylate
Kim, J. K., Kim, Y.-J., Fillmore, J. J., Chen, Y., Moore, I., Lee, J., Yuan, M., Li, Z. W., Karin, M., Perret, P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11559 · Cited by 737 · see citing works
Bouatia-Naji, N., Bonnefond, A., Cavalcanti-Proença, C., Sparsø, T., Holmkvist, J., Marchand, M., Delplanque, J., Lobbens, S., Rocheleau, G., Durand, E., et al. (2009) · Nature Genetics · doi:10.1038/ng.277 · Cited by 611 · see citing works
Accurate Assessment of β-Cell Function
Bergman, R. N., Ader, M., Hücking, K., & Citters, G. V. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s212 · Cited by 517 · see citing works
Ravassard, P., Hazhouz, Y., Pechberty, S., Bricout-Neveu, E., Armanet, M., Czernichow, P., & Scharfmann, R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58447 · Cited by 504 · see citing works
Fadista, J., Vikman, P. J., Ottosson-Laakso, E., Mollet, I. G., Esguerra, J. L. S., Taneera, J., Storm, P., Osmark, P., Ladenvall, C., Prasad, R. B., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402665111 · Cited by 470 · see citing works
Hanson, R. L., Pratley, R. E., Bogardus, C., Narayan, K. M. V., Roumain, J. M. L., Imperatore, G., Fagot-Campagna, A., Pettitt, D. J., Bennett, P. H., & Knowler, W. C. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010187 · Cited by 463 · see citing works
Genetics of Type 2 Diabetes—Pitfalls and Possibilities
Prasad, R., & Groop, L. (2015) · Genes · doi:10.3390/genes6010087 · Cited by 458 · see citing works
Mammalian melatonin receptors: molecular biology and signal transduction
von Gall, C., Stehle, J. H., & Weaver, D. R. (2002) · Cell and Tissue Research · doi:10.1007/s00441-002-0581-4 · Cited by 455 · see citing works
Gaulton, K. J., Ferreira, T. C., Lee, Y., Raimondo, A., Mägi, R., Reschen, M. E., Mahajan, A., Locke, A. E., Rayner, N. W., Robertson, N., et al. (2015) · Nature Genetics · doi:10.1038/ng.3437 · Cited by 390 · see citing works
Blodgett, D. M., Nowosielska, A., Afik, S., Pechhold, S., Cura, A. J., Kennedy, N. J., Kim, S., Kucukural, A., Davis, R. J., Kent, S. C., et al. (2015) · Diabetes · doi:10.2337/db15-0039 · Cited by 330 · see citing works
Oscillations of cyclic AMP in hormone-stimulated insulin-secreting β-cells
Dyachok, O., Isakov, Y., Sågetorp, J., & Tengholm, A. (2006) · Nature · doi:10.1038/nature04410 · Cited by 247 · see citing works
Targeted Disruption of the Mouse Mel1b Melatonin Receptor
Jin, X., von Gall, C., Pieschl, R. L., Gribkoff, V. K., Stehle, J. H., Reppert, S. M., & Weaver, D. R. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.1054-1060.2003 · Cited by 240 · see citing works
Function and expression of melatonin receptors on human pancreatic islets
Ramracheya, R. D., Muller, D. S., Squires, P. E., Brereton, H., Sugden, D., Huang, G. C., Amiel, S. A., Jones, P. M., & Persaud, S. J. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00523.x · Cited by 186 · see citing works
Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening
Rubio-Sastre, P., Scheer, F. A. J. L., Gómez-Abellán, P., Madrid, J. A., & Garaulet, M. (2014) · SLEEP · doi:10.5665/sleep.4088 · Cited by 180 · see citing works
Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene
Mulder, H., Nagorny, C. L. F., Lyssenko, V., & Groop, L. (2009) · Diabetologia · doi:10.1007/s00125-009-1359-y · Cited by 169 · see citing works
Glucose- and Hormone-Induced cAMP Oscillations in α- and β-Cells Within Intact Pancreatic Islets
Tian, G., Sandler, S., Gylfe, E., & Tengholm, A. (2011) · Diabetes · doi:10.2337/db10-1087 · Cited by 128 · see citing works
Kemp, D. M., Ubeda, M., & Habener, J. F. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00064-3 · Cited by 122 · see citing works
Experimental and clinical aspects of melatonin and clock genes in diabetes
Peschke, E., Bähr, I., & Mühlbauer, E. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12240 · Cited by 111 · see citing works
Rönn, T., Wen, J., Yang, Z., Lü, B., Du, Y., Groop, L., Hu, R., & Ling, C. (2009) · Diabetologia · doi:10.1007/s00125-009-1297-8 · Cited by 108 · see citing works
Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle
Teodoro, B. G., Baraldi, F. G., Sampaio, I. H., Bomfim, L. H. M., Queiroz, A. L., Passos, M. A., Carneiro, E. M., Alberici, L. C., Gomis, R., Amaral, F. G., et al. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12157 · Cited by 106 · see citing works
Garaulet, M., Gómez-Abellán, P., Rubio-Sastre, P., Madrid, J. A., Saxena, R., & Scheer, F. A. J. L. (2015) · Metabolism · doi:10.1016/j.metabol.2015.08.003 · Cited by 100 · see citing works
Jonsson, A. E., Ladenvall, C., Ahluwalia, T. S., Kravić, J., Krus, U., Taneera, J., Isomaa, B., Tuomilehto, J., Renström, E., Groop, L., et al. (2013) · Diabetes · doi:10.2337/db12-1627 · Cited by 98 · see citing works
Parallel signaling pathways of melatonin in the pancreatic β‐cell
Peschke, E., Bach, A. G., & Mühlbauer, E. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2005.00297.x · Cited by 82 · see citing works
Isomaa, B., Forsén, B., Lahti, K., Holmström, N., Wadén, J., Matintupa, O., Almgren, P., Eriksson, J. G., Lyssenko, V., Taskinen, M., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1776-y · Cited by 77 · see citing works
Characterization of Stimulus-Secretion Coupling in the Human Pancreatic EndoC-βH1 Beta Cell Line
Andersson, L. E., Valtat, B., Bagge, A., Sharoyko, V. V., Nicholls, D. G., Ravassard, P., Scharfmann, R., Spégel, P., & Mulder, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120879 · Cited by 74 · see citing works
Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist
Tang, Y., Axelsson, A. S., Spégel, P., Andersson, L. E., Mulder, H., Groop, L., Renström, E., & Rosengren, A. H. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009934 · Cited by 74 · see citing works
Fex, M., Nitert, M. D., Wierup, N., Sundler, F., Ling, C., & Mulder, H. (2006) · Diabetologia · doi:10.1007/s00125-006-0464-4 · Cited by 71 · see citing works
Clock genes and metabolic disease
Marcheva, B., Ramsey, K. M., Affinati, A. H., & Bass, J. T. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00698.2009 · Cited by 71 · see citing works
Distribution of melatonin receptors in murine pancreatic islets
Nagorny, C. L. F., Sathanoori, R., Voss, U., Mulder, H., & Wierup, N. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00859.x · Cited by 55 · see citing works
Influence of melatonin receptor signalling on parameters involved in blood glucose regulation
Bazwinsky‐Wutschke, I., Bieseke, L., Mühlbauer, E., & Peschke, E. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12100 · Cited by 50 · see citing works
Mühlbauer, E., Albrecht, E., Bazwinsky‐Wutschke, I., & Peschke, E. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.00959.x · Cited by 50 · see citing works
Mühlbauer, E., Albrecht, E., Hofmann, K., Bazwinsky‐Wutschke, I., & Peschke, E. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00898.x · Cited by 46 · see citing works
Renström, F., Koivula, R. W., Varga, T. V., Hallmans, G., Mulder, H., Florez, J. C., Hu, F. B., & Franks, P. W. (2015) · Diabetologia · doi:10.1007/s00125-015-3533-8 · Cited by 37 · see citing works
Genome wide association studies for diabetes: perspective on results and challenges
Torres, J., Cox, N. J., & Philipson, L. H. (2013) · Pediatric Diabetes · doi:10.1111/pedi.12015 · Cited by 33 · see citing works
Determining predictors of response to exenatide in type 2 diabetes
Anderson, S. L., Trujillo, J. M., McDermott, M., & Saseen, J. J. (2012) · Journal of the American Pharmacists Association · doi:10.1331/japha.2012.10217 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Transcriptional architecture of the mammalian circadian clock
Takahashi, J. S. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.150 · Cited by 2,639 · see citing works
Circadian physiology of metabolism
Panda, S. (2016) · Science · doi:10.1126/science.aah4967 · Cited by 1,092 · see citing works
Circadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733 · see citing works
Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures
Potter, G. D., Skene, D. J., Arendt, J., Cade, J. E., Grant, P. J., & Hardie, L. J. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1083 · Cited by 729 · see citing works
“Melatonin may have important roles in metabolic regulation, perhaps helping prevent nocturnal hypoglycemia by inhibiting insulin secretion (141).”
Melatonin as a Hormone: New Physiological and Clinical Insights
Cipolla‐Neto, J., & do Amaral, F. G. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00084 · Cited by 653 · see citing works
Mechanisms controlling pancreatic islet cell function in insulin secretion
Campbell, J. E., & Newgard, C. B. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00317-7 · Cited by 631 · see citing works
Melatonin and inflammation-Story of a double-edged blade
Hardeland, R. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12525 · Cited by 455 · see citing works
Lunn, R. M., Blask, D. E., Coogan, A. N., Figueiro, M. G., Gorman, M. R., Hall, J. E., Hansen, J., Nelson, R. J., Panda, S., Smolensky, M. H., et al. (2017) · Science of The Total Environment · doi:10.1016/j.scitotenv.2017.07.056 · Cited by 402 · see citing works
“The recent discovery that melatonin can adversely affect glucose-induced insulin release from the pancreas raises a mechanistic link between melatonin and metabolism (Tuomi et al., 2016).”
BackgroundTime-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases
Chaix, A., Manoogian, E. N. C., Melkani, G. C., & Panda, S. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124320 · Cited by 402 · see citing works
“This also fits with the action of circadian rhythms in insulin release and the suppressive effect of the sleep hormone melatonin on insulin release (92, 110, 122).”
BackgroundTime-restricted eating for the prevention and management of metabolic diseases
Manoogian, E. N. C., Chow, L. S., Taub, P. R., Laferrère, B., & Panda, S. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab027 · Cited by 344 · see citing works
“At night, the rise in melatonin before bedtime can inhibit glucoseinduced insulin release from the pancreatic β cells (48).”
BackgroundMelatonin receptors: molecular pharmacology and signalling in the context of system bias
Cecon, E., Oishi, A., & Jockers, R. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13950 · Cited by 286 · see citing works
“Taken together with other experimental findings, a model was proposed based on the assumption that MT2 protein levels are increased, exaggerating the putative inhibitory effect of melatonin on pancreatic insulin production in risk allele carriers (Tuomi et al., 2016).”
ResultMelatonin in type 2 diabetes mellitus and obesity
Karamitri, A., & Jockers, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0130-1 · Cited by 268 · see citing works
Genetics of circadian rhythms and sleep in human health and disease
Lane, J. M., Qian, J., Mignot, E., Redline, S., Scheer, F. A. J. L., & Saxena, R. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00519-z · Cited by 236 · see citing works
cAMP signalling in insulin and glucagon secretion
Tengholm, A., & Gylfe, E. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12993 · Cited by 223 · see citing works
Timing of breakfast, lunch, and dinner. Effects on Obesity and Metabolic Risk
Lopez-Minguez, J., Gómez-Abellán, P., & Garaulet, M. (2019) · Nutrients · doi:10.3390/nu11112624 · Cited by 201 · see citing works
“This demonstrated that melatonin is implicated in the detrimental effects of eating late at night when melatonin levels are normally high [27,49].”
BackgroundMelatonin effects on glucose metabolism: time to unlock the controversy
Garaulet, M., Qian, J., Florez, J. C., Arendt, J., Saxena, R., & Scheer, F. A. J. L. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.11.011 · Cited by 193 · see citing works
“First, GWAS have shown that the rs10830963 risk variant of MTNR1B , which confers increased expression of the receptor in human pancreatic islets [15], is associated with impaired fasting glucose, measures of decreased insulin secretion and increased T2D risk [15–20].”
BackgroundGenetic variant effects on gene expression in human pancreatic islets and their implications for T2D
Viñuela, A., Varshney, A., van de Bunt, M., Prasad, R. B., Asplund, O., Bennett, A., Boehnke, M., Brown, A. A., Erdos, M. R., Fadista, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18581-8 · Cited by 152 · see citing works
Light exposure during sleep impairs cardiometabolic function
Mason, I. C., Grimaldi, D., Reid, K. J., Warlick, C., Malkani, R. G., Abbott, S. M., & Zee, P. C. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113290119 · Cited by 151 · see citing works
Xu, H., Du, X., Xu, J., Zhang, Y., Tian, Y., Liu, G., Wang, X., Ma, M., Du, W., Liu, Y., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000603 · Cited by 147 · see citing works
“β cell mass β cell mass was measured as described previously [75].”
MethodOff the Clock: From Circadian Disruption to Metabolic Disease
Maury, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071597 · Cited by 142 · see citing works
“In particular, these studies described the impact of the MTNR1B (melatonin receptor 1B) polymorphism on fasting glucose or insulin-secretion-related traits and on T2D risk [135–138], which might be explained by the impact of melatonin signaling on insulin secretion [139].”
BackgroundAkkermansia muciniphila : is it the Holy Grail for ameliorating metabolic diseases?
Yan, J., Sheng, L., & Li, H. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1984104 · Cited by 142 · see citing works
Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A randomized, cross-over study
Lopez-Minguez, J., Saxena, R., Bandín, C., Scheer, F. A., & Garaulet, M. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2017.04.003 · Cited by 124 · see citing works
“Results of the current study have clinical and public health relevance given that: a) the risk G allele is highly prevalent, with ~51% of individuals of European ancestry being carriers of the G allele (MAF ~30%); b) risk carriers have enhanced expression of the melatonin receptor 1b in pancreatic islets [9,13] implic…”
Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics
Krentz, N. A. J., & Gloyn, A. L. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0325-0 · Cited by 128 · see citing works
Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism
Owino, S., Buonfiglio, D. D. C., Tchio, C. I. M., & Tosini, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00488 · Cited by 124 · see citing works
“MT2 KO mice, which previously lacked a clear metabolic phenotype, were recently reported to display decreased hepatic insulin sensitivity and increased insulin secretion (34).”
BackgroundMelatonin and the pathologies of weakened or dysregulated circadian oscillators
Hardeland, R. (2016) · Journal of Pineal Research · doi:10.1111/jpi.12377 · Cited by 111 · see citing works
“In beta cells, the G allele is overexpressed compared to the wildtype allele, a change that causes a more profound decrease of cAMP and, therefore, suppresses more strongly the cAMPdependent secretion of insulin.(186-189) Moreover, the presence of the G allele was shown to worsen the reduction of glucose tolerance by…”
BackgroundG Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus
Riddy, D. M., Delerive, P., Summers, R. J., Sexton, P. M., & Langmead, C. J. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014373 · Cited by 108 · see citing works
“As described above, there is close homology between FFAR2 and FFAR3, and therefore, FFAR3 is activated by similar SCFAs, including formate, acetate, propionate, and butyrate (Ulven, 2012), although the rank orders differ between the receptors.”
BackgroundConnecting insufficient sleep and insomnia with metabolic dysfunction
Duan, D., Kim, L. J., Jun, J. C., & Polotsky, V. Y. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14926 · Cited by 110 · see citing works
Gupta, N. J., Kumar, V., & Panda, S. (2017) · PLOS ONE · doi:10.1371/journal.pone.0172852 · Cited by 100 · see citing works
Song, S. O., He, K., Narla, R. R., Kang, H. G., Ryu, H. U., & Boyko, E. J. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2018.0256 · Cited by 101 · see citing works
Ren, S., Rutto, L. K., & Katuuramu, D. N. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221687 · Cited by 100 · see citing works
Physiological and pharmacological perspectives of melatonin
Samanta, S. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1770799 · Cited by 106 · see citing works
“Night-time melatonin exerts inhibitory effect on insulin secretion and prevents nocturnal hypoglycaemia (Tuomi et al. 2016).”
BackgroundMembrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease
Nikolaev, G., Robeva, R. N., & Konakchieva, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010471 · Cited by 96 · see citing works
Pugliese, G., Barrea, L., Laudisio, D., Salzano, C., Aprano, S., Colao, A., Savastano, S., & Muscogiuri, G. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00369-y · Cited by 94 · see citing works
Circadian blueprint of metabolic pathways in the brain
Greco, C. M., & Sassone‐Corsi, P. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0096-y · Cited by 93 · see citing works
Circadian desynchrony and glucose metabolism
Speksnijder, E. M., Bisschop, P. H. L. T., Siegelaar, S. E., Stenvers, D. J., & Kalsbeek, A. (2024) · Journal of Pineal Research · doi:10.1111/jpi.12956 · Cited by 98 · see citing works
“177 However, randomized controlled trials in humans found no effect of melatonin supplementation on glucose ‐ stimulated insulin secretion, 178 but a decreased insulin sensitivity index in healthy men upon a high daytime dose of melatonin, 179 and reduced whole ‐ body insulin sensitivity after 3…”
BackgroundOwino, S., Sánchez‐Bretaño, A., Tchio, C. I. M., Cecon, E., Karamitri, A., Dam, J., Jockers, R., Piccione, G. G., Noh, H. L., Kim, T., et al. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12462 · Cited by 85 · see citing works
The role of melatonin in the treatment of type 2 diabetes mellitus and Alzheimer's disease
Shen, S., Liao, Q., Wong, Y. K., Chen, X., Yang, C., Xu, C., Sun, J., & Wang, J. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.66871 · Cited by 84 · see citing works
“It has been shown that disturbance of melatonin signaling is implicated in development of T2DM raised by IR [39-42].”
BackgroundOttosson-Laakso, E., Krus, U., Storm, P., Prasad, R. B., Oskolkov, N., Ahlqvist, E., Fadista, J., Hansson, O., Groop, L., & Vikman, P. J. (2017) · Diabetes · doi:10.2337/db17-0311 · Cited by 84 · see citing works
“The SNP rs10830963, which is one of the strongest eQTLs for the melatonin receptor 1B gene (MTNR1B) in human islets (30) was nominally associated with CIR (G allele, b =20.”
BackgroundRole of the Circadian Clock in the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease
Shetty, A., Hsu, J. W., Manka, P. P., & Syn, W. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-018-5242-x · Cited by 82 · see citing works
Neurogenetic basis for circadian regulation of metabolism by the hypothalamusPreprint
Cedernaes, J., Waldeck, N. J., & Bass, J. T. (2019) · Genes & Development · doi:10.1101/gad.328633.119 · Cited by 84 · see citing works
“Since melatonin receptors are expressed in pancreatic β cells, it has been proposed that melatonin may mediate glucose homeostasis through direct control of insulin secretion (Cipolla-Neto et al. 2014) in β cells (Tuomi et al. 2016).”
BackgroundHuman Genetics of Obesity and Type 2 Diabetes Mellitus
Ingelsson, E., & McCarthy, M. I. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.118.002090 · Cited by 83 · see citing works
Bysani, M., Ågren, R., Davegårdh, C., Volkov, P., Rönn, T., Unneberg, P., Bacos, K., & Ling, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-44076-8 · Cited by 81 · see citing works
Simon, S. L., McWhirter, L., Diniz Behn, C., Bubar, K. M., Kaar, J. L., Pyle, L., Rahat, H., Garcia-Reyes, Y., Carreau, A.-M., Wright, K. P., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02385 · Cited by 87 · see citing works
Chronomedicine and type 2 diabetes: shining some light on melatonin
Forrestel, A. C., Miedlich, S. U., Yurcheshen, M. E., Wittlin, S. D., & Sellix, M. T. (2016) · Diabetologia · doi:10.1007/s00125-016-4175-1 · Cited by 80 · see citing works
“the risk of developing diabetes among those carrying the MNTR1B risk allele [28, 29, 138, 165].”
BackgroundInfluentialGaraulet, M., Lopez-Minguez, J., Dashti, H. S., Vetter, C., Hernández-Martínez, A. M., Pérez-Ayala, M., Baraza, J. C., Wang, W., Florez, J. C., Scheer, F. A. J. L., et al. (2022) · Diabetes Care · doi:10.2337/dc21-1314 · Cited by 77 · see citing works
Aiding sleep in type 2 diabetes: therapeutic considerations
Tan, X., van Egmond, L., Chapman, C. D., Cedernaes, J., & Benedict, C. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30233-4 · Cited by 72 · see citing works
Onphachanh, X., Lee, H. J., Lim, J. R., Jung, Y. H., Kim, J. S., Chae, C. W., Lee, S., Gabr, A. A., & Han, H. J. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12427 · Cited by 71 · see citing works
Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Corbin, L. J., Tan, V. Y., Hughes, D. A., Wade, K. H., Paul, D. S., Tansey, K. E., Butcher, F. C., Dudbridge, F., Howson, J. M. M., Jallow, M. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03109-y · Cited by 66 · see citing works
CC-401 Promotes β-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition
Abdolazimi, Y., Zhao, Z., Lee, S., Xu, H., Allegretti, P. A., Horton, T. M., Yeh, B. T., Moeller, H. P., Nichols, R. J., McCutcheon, D., et al. (2018) · Endocrinology · doi:10.1210/en.2018-00083 · Cited by 68 · see citing works
New insights into the role of melatonin in plants and animals
Agathokleous, E., Kitao, M., & Calabrese, E. J. (2018) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2018.12.008 · Cited by 67 · see citing works
Melatonin, mitochondria, and the metabolic syndrome
Cardinali, D. P., & Vigo, D. E. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2611-0 · Cited by 70 · see citing works
“Melatonin treatment reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers, indicating that an increased melatonin signaling may be a risk factor for type 2 diabetes [157].”
Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications
Lee, J., Lee, N. K., & Moon, J. H. (2025) · Endocrinology and Metabolism · doi:10.3803/enm.2024.2264 · Cited by 72 · see citing works
“Overexpression of MTN-R1B in insulin-secreting β-cells significantly enhances the in - hibitory effect of melatonin on insulin release, primarily by reducing cyclic adenosine monophosphate levels, a critical signaling molecule for insulin secretion [55].”
Serotonergic regulation of insulin secretion
Cataldo, L. R., Lyons, C., Bennet, H., Artner, I., & Fex, M. (2018) · Acta Physiologica · doi:10.1111/apha.13101 · Cited by 64 · see citing works
Continuous Alertness Assessments
Tag, B., Vargo, A. W., Gupta, A., Chernyshov, G., Kunze, K. S., & Dingler, T. (2019) · CHI Conference on Human Factors in Computing Systems · doi:10.1145/3290605.3300694 · Cited by 63 · see citing works
“While a biological rhythm, which is chronically out of sync, can cause serious health problems [18, 65], time-of-day variations have a significant impact on our everyday cognitive performance [56] affecting alertness and fatigue levels.”
BackgroundKaramitri, A., Plouffe, B., Bonnefond, A., Chen, M., Gallion, J., Guillaume, J.-L., Hegron, A., Boissel, M., Canouil, M., Langenberg, C., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aan6622 · Cited by 62 · see citing works
“Functional studies on the common SNP rs10830963, located in the intron of MTNR1B, showed a twofold increase in MTNR1B mRNA abundance in human pancreatic islets of GG T2D risk allele carriers (9).”
BackgroundPoor Quality Control of Over-the-Counter Melatonin: What They Say Is Often Not What You Get
Grigg-Damberger, M. M., & Ianakieva, D. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6434 · Cited by 62 · see citing works
“16,17 Melatonin appears to inhibit nocturnal insulin release, 18 and long-term use of prolonged-release melatonin in patients with type 2 diabetes mellitus had a beneficial effect on their hemoglobin A1c levels.”
Tan, D. X., & Hardeland, R. (2020) · Molecules · doi:10.3390/molecules25194410 · Cited by 60 · see citing works
Carbamate Insecticides Target Human Melatonin Receptors
Popovska‐Gorevski, M., Dubocovich, M. L., & Rajnarayanan, R. V. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00301 · Cited by 60 · see citing works
The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis
Mazzoccoli, G., Cosmo, S. D., & Mazza, T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00193 · Cited by 59 · see citing works
“…response of energy expenditure to weight-loss diets (measured as respiratory quotient and resting metabolic rate) in carriers of CRY2 rs11605924 variant as well as rs10830963G allele of MTNR1B gene, encoding the MT2 melatonin receptor (Mirzaei et al., 2014; Lane et al., 2016; Tuomi et al., 2016).”
BackgroundDiabetes mellitus and melatonin: Where are we?
Patel, R., PARMAR, N. R., Palit, S. P., RATHWA, N. N., Ramachandran, A. V., & Begum, R. (2022) · Biochimie · doi:10.1016/j.biochi.2022.01.001 · Cited by 58 · see citing works
Alver, M., Palover, M., Saar, A., Läll, K., Zekavat, S. M., Tõnisson, N., Leitsalu, L., Reigo, A., Nikopensius, T., Ainla, T., et al. (2018) · Genetics in Medicine · doi:10.1038/s41436-018-0311-2 · Cited by 56 · see citing works
Thomas, A. P., Hoang, J. D., Vongbunyong, K. E., Nguyen, A., Rakshit, K., & Matveyenko, A. V. (2016) · Endocrinology · doi:10.1210/en.2016-1309 · Cited by 54 · see citing works
“Indeed, increased expression of MTNR1B in human -cells attenuates GSIS consistent with acute effects of melatonin on reducing cAMP levels and potential physiological role in restraining nighttime insulin release (52, 53).”
BackgroundGubin, D. G., Nelaeva, A. A., Uzhakova, A. E., Хасанова, Ю. В., Cornélissen, G., & Weinert, D. (2017) · Chronobiology International · doi:10.1080/07420528.2017.1347670 · Cited by 54 · see citing works
“Genetic polymorphismmay be particularly important as some patients may be predisposed to have a pancreas that is sensitive to insulin-inhibiting effects of nocturnal melatonin (Tuomi et al., 2016).”
BackgroundPleiotropic Effects of Melatonin
Mahmood, D. (2019) · Drug Research · doi:10.1055/a-0656-6643 · Cited by 52 · see citing works
“, also suggested that melatonin physiologically could inhibit insulin release during the nighttime.[68] Previously, McMullan et al.”
BackgroundHu, S., Hu, C., Luo, L., Zhang, H., Zhao, S., Liu, Z., & Zeng, L. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.133500 · Cited by 46 · see citing works
Human Pluripotent Stem Cells to Model Islet Defects in Diabetes
Balboa, D., Iworima, D. G., & Kieffer, T. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.642152 · Cited by 47 · see citing works
“A genetic variant increasing the expression of MTNR1B has been shown to lower cAMP levels in beta cells, leading to reduced insulin secretion (68).”
BackgroundPace, N. P., Vassallo, J., & Calleja‐Agius, J. (2020) · Early Human Development · doi:10.1016/j.earlhumdev.2020.105219 · Cited by 45 · see citing works
Buonfiglio, D. D. C., Tchio, C. I. M., Furigo, I. C., Donato, J., Baba, K., Cipolla‐Neto, J., & Tosini, G. (2019) · Journal of Pineal Research · doi:10.1111/jpi.12580 · Cited by 43 · see citing works
Melatonin Uptake by Cells: An Answer to Its Relationship with Glucose?
Mayo, J. C., Aguado, A. I. W., Cernuda‐Cernuda, R., Álvarez-Artime, A., Cepas, V., Quirós-González, I., Hevia, D., & Sainz, R. M. (2018) · Molecules · doi:10.3390/molecules23081999 · Cited by 41 · see citing works
“However, whether this is due as has been suggested to an excess of melatonin signaling [175] or rather, on the contrary, to a defective receptor function is still a matter of debate [176].”
BackgroundAssociations between chronotype, MTNR1B genotype and risk of type 2 diabetes in UK Biobank
Tan, X. W., Ciuculete, D. M., Schiöth, H. B., & Benedict, C. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12994 · Cited by 41 · see citing works
Zhu, H., Zhao, Z., Liu, H., Cai, J., Lu, Q., Ji, L., & Xu, J. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2191218 · Cited by 41 · see citing works
“thesis; cAMP is a stimulator of insulin release [18].”
BackgroundFrom Genetic Association to Molecular Mechanisms for Islet-cell Dysfunction in Type 2 Diabetes
Mattis, K. K., & Gloyn, A. L. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.045 · Cited by 39 · see citing works
McHill, A. W., Hull, J. T., McMullan, C. J., & Klerman, E. B. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00319 · Cited by 38 · see citing works
“In addition, protocols providing exogenous melatonin have found decreases in insulin secretion and sensitivity (56, 57), and individuals carrying a common variant in the melatonin receptor 1b gene have increased risk for impaired glucose regulation (58, 59), further supporting the hypothesis relating the circadian tim…”
BackgroundSkawratananond, S., Xiong, D. X., Zhang, C., Tonk, S. S., Pinili, A., Delacruz, B., Pham, P., Smith, S. C., Navab, R., & Reddy, P. H. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102732 · Cited by 39 · see citing works
Untimely oxidative stress in β-cells leads to diabetes – Role of circadian clock in β-cell function
Lee, J. M., Ma, K., Moulik, M., & Yechoor, V. K. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.022 · Cited by 39 · see citing works
Goñi, L., Sun, D., Heianza, Y., Wang, T., Huang, T., Martínez, J. A., Shang, X., Bray, G. A., Smith, S. R., Sacks, F. M., et al. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1660-y · Cited by 36 · see citing works
Lined multifocal wearers prefer progressive addition lenses.
Boroyan, H. J., Cho, M. H., Fuller, B., Krefman, R. A., McDougall, J., Schaeffer, J. L., & Tahran, R. (1995) · PubMed · Cited by 35 · see citing works
Pfeffer, M., von Gall, C., Wicht, H., & Korf, H. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.883637 · Cited by 36 · see citing works
“Another more recent study reported a decreased hepatic insulin sensitivity and an increased insulin secretion in MT2 KOmice (Tuomi et al., 2016).”
BackgroundQiu, X., Liang, T., Wu, Z., Zhu, Y., Gao, W., Gao, B., Qiu, J., Wang, X., Chen, T., Deng, Z., et al. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.65973 · Cited by 34 · see citing works
“Melatonin receptor signaling pathways have been found to be related to several diseases, such as type II diabetes mellitus[52], multiple sclerosis[53] and tumor recurrence[54].”
BackgroundSleep Control, GPCRs, and Glucose Metabolism
Tsuneki, H., Sasaoka, T., & Sakurai, T. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.06.011 · Cited by 34 · see citing works
“An increase in the expression of the MT2 receptor found in the islets of humans with a common diabetes risk variant in MTNR1B (rs10830963) was found to enhance the melatonin-induced inhibition of insulin release in insulin-secreting cells [62].”
BackgroundReutrakul, S., Siwasaranond, N., Nimitphong, H., Saetung, S., Chirakalwasan, N., Chailurkit, L., Srijaruskul, K., Ongphiphadhanakul, B., & Thakkinstian, A. (2017) · Chronobiology International · doi:10.1080/07420528.2016.1278382 · Cited by 33 · see citing works
“However, positive effects of melatonin on glucose metabolism were not unanimous as a recent study revealed that melatonin blocks insulin release in mouse islets and clonal insulin-secreting cells (Tuomi et al., 2016).”
BackgroundShah, N. Z., Abdalla, M. A., Deshmukh, H., & Sathyapalan, T. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211042145 · Cited by 38 · see citing works
Building Cognition-Aware Systems
Dingler, T., Schmidt, A., & Machulla, T. (2017) · Proceedings of the ACM on Interactive Mobile Wearable and Ubiquitous Technologies · doi:10.1145/3132025 · Cited by 33 · see citing works
“Chronically high levels of mental load and circadian disruptions can further lead to depression, burnout, and even diabetes [31].”
BackgroundMelatonin signalling and type 2 diabetes risk: too little, too much or just right?
Mulder, H. (2017) · Diabetologia · doi:10.1007/s00125-017-4249-8 · Cited by 33 · see citing works
Association of melatonin & MTNR1B variants with type 2 diabetes in Gujarat population
Patel, R., RATHWA, N. N., Palit, S. P., Ramachandran, A. V., & Begum, R. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.04.058 · Cited by 32 · see citing works
A new prospective on the role of melatonin in diabetes and its complications
Mok, J. X., Ooi, J. H., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2019) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2019-0036 · Cited by 33 · see citing works
Harmsen, J., Wefers, J., Doligkeit, D., Schlangen, L. J. M., Dautzenberg, B., Rense, P., van Moorsel, D., Hoeks, J., Moonen‐Kornips, E., Gordijn, M. C. M., et al. (2022) · Diabetologia · doi:10.1007/s00125-021-05643-9 · Cited by 33 · see citing works
Melatonin in energy control: Circadian time‐giver and homeostatic monitor
Challet, É., & Pévet, P. (2024) · Journal of Pineal Research · doi:10.1111/jpi.12961 · Cited by 34 · see citing works
“99 Temporal mismatches between the nocturnal secretion of pineal melatonin and the daily feeding/fasting cycle may have deleterious effects on human glycemic control.”
BackgroundWhat do we really know about the safety and efficacy of melatonin for sleep disorders?
Kennaway, D. J. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.2000714 · Cited by 31 · see citing works
Bonnefond, A., & Froguel, P. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0957-1 · Cited by 29 · see citing works
Bermejo-Millo, J. C., Guimarães, M. R. M., de Luxán‐Delgado, B., Potes, Y., Pérez-Martínez, Z., Díaz-Luis, A., Caballero, B., Solano, J. J., Vega‐Naredo, I., & Coto‐Montes, A. M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0967-2 · Cited by 27 · see citing works
“These findings are underpinned by the effects of a gain of function mutation (BG allele^) of the melatonin receptor gene MTNR1B, which is prodiabetic, after overexpression in pancreatic beta cells [66, 67].”
BackgroundEspino, J., Rodríguez, A. B., & Pariente, J. A. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180410094149 · Cited by 29 · see citing works
Xia, A., Zhu, H., Zhao, Z., Liu, H., Wang, P.-H., Ji, L., & Xu, J. (2023) · Nutrients · doi:10.3390/nu15061406 · Cited by 28 · see citing works
“Studies have revealed that the rs10830963G allele greatly enhances the expression of MT2 [58,60–62], with NEUROD1 and FOXA2 [22,63] serving as two important transcription factors in this process.”
BackgroundInfluentialThe case for too little melatonin signalling in increased diabetes risk
Bonnefond, A., & Froguel, P. (2017) · Diabetologia · doi:10.1007/s00125-017-4255-x · Cited by 28 · see citing works
Li‐Gao, R., Hughes, D. A., van Klinken, J. B., de Mutsert, R., Rosendaal, F. R., Mook-Kanamori, D. O., Timpson, N. J., & van Dijk, K. W. (2021) · Diabetes · doi:10.2337/db21-0397 · Cited by 28 · see citing works
“The G-allele carriers exhibited a stronger inhibition of insulin secretion after melatonin treatment (43).”
BackgroundSchwartsburd, P. M. (2017) · Future Science OA · doi:10.4155/fsoa-2017-0015 · Cited by 27 · see citing works
Circadian Clock-Controlled Checkpoints in the Pathogenesis of Complex Disease
Li, M., Xin, H., Yuan, Y., Yang, X., Li, H., Tian, D., Zhang, H., Zhang, Z., Han, T.-L., Chen, Q., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.721231 · Cited by 29 · see citing works
Distribution and density of melatonin receptors in human main pancreatic islet cell types
Zibolka, J., Bazwinsky‐Wutschke, I., Mühlbauer, E., & Peschke, E. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12480 · Cited by 27 · see citing works
Pancreatic Islet Transcriptional Enhancers and Diabetes
Cebola, I. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1230-6 · Cited by 25 · see citing works
A Wake-up Call for Type 2 Diabetes?
Persaud, S. J., & Jones, P. M. (2016) · New England Journal of Medicine · doi:10.1056/nejmcibr1607950 · Cited by 25 · see citing works
- Authors
- Tuomi, T., Nagorny, C. L. F., Singh, P., Bennet, H., Yu, Q., Alenkvist, I., Isomaa, B., Östman, B., Söderström, J., Pesonen, A.-K., Martikainen, S., Räikkönen, K., Forsén, T., Hakaste, L., Almgren, P., Storm, P., Asplund, O., Shcherbina, L., Fex, M., Fadista, J., Tengholm, A., Wierup, N., Groop, L., & Mulder, H.
- Affiliations
- Lund University (SE)
- Uppsala University (SE)
- University of Helsinki (FI)
- Folkhälsans Forskningscentrum (FI)
- Corresponding author
- Mulder, Hindrik
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 1067-1077
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2367683267
- Cited by
- 262
- References
- 44
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 20 · 2023: 17 · 2022: 17 · 2021: 28 · 2020: 29 · 2019: 27 · 2018: 36 · 2017: 30 · 2016: 13
- FWCI
- 39.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Finska Läkaresällskapet
- Folkhälsanin Tutkimussäätiö
- European Foundation for the Study of Diabetes
- Lunds Universitet (2009-1039)
- Novo Nordisk
- Signe ja Ane Gyllenbergin Säätiö
- Vetenskapsrådet (349-2006-237, 325‐2012‐6778, 2010-03490, 521-2012-2119, 2006–237, 2009-1039, 521-2010-3490)
- Samfundet Folkhälsan
- Sigrid Juséliuksen Säätiö
- Svenska Kulturfonden
- Paavo Nurmen Säätiö
- Novo Nordisk Fonden (NNF14OC0010995, NNF14OC0010363)
- Diabetestutkimussäätiö
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, melatonin signaling, MTNR1B, insulin secretion, pancreatic islets, cyclic AMP, genetic risk variants, hyperglycemia, melatonin treatment
- MeSH terms
- Insulin Secretion, Cyclic AMP, Animals, Diabetes Mellitus, Type 2, Glucose, Heterozygote, Humans, Insulin, Melatonin, Risk Factors, Signal Transduction, Mice, Knockout, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptors, Melatonin, Insulin-Secreting Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
