2,962
Views
5
CrossRef citations to date
0
Altmetric
Endocrinology

The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story

ORCID Icon, , , , , & show all
Pages 1262-1286 | Received 02 Jan 2023, Accepted 10 Mar 2023, Published online: 28 Mar 2023

References

  • International Diabetes Federation (IDF) 2021. Available from: https://diabetesatlasorg/.
  • Smushkin G, Vella A. Genetics of type 2 diabetes. Curr Opin Clin Nutr Metab Care. 2010;13(4):471–477.
  • Panda S. Circadian physiology of metabolism. Science. 2016;354(6315):1008–1015.
  • Qian J, Scheer F. Circadian system and glucose metabolism: implications for physiology and disease. Trends Endocrinol Metab. 2016;27(5):282–293.
  • Mason IC, Qian J, Adler GK, et al. Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetologia. 2020;63(3):462–472.
  • Shan Z, Li Y, Zong G, et al. Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses. BMJ. 2018;363:k4641.
  • Pan A, Schernhammer ES, Sun Q, et al. Rotating night shift work and risk of type 2 diabetes: two prospective cohort studies in women. PLoS Med. 2011;8(12):e1001141.
  • Suwazono Y, Sakata K, Okubo Y, et al. Long-term longitudinal study on the relationship between alternating shift work and the onset of diabetes mellitus in male japanese workers. J Occup Environ Med. 2006;48(5):455–461.
  • Koopman ADM, Rauh SP, van ‘t Riet E, et al. The association between social jetlag, the metabolic syndrome, and type 2 diabetes mellitus in the general population: the new hoorn study. J Biol Rhythms. 2017;32(4):359–368.
  • Mota MC, Silva CM, Balieiro LCT, et al. Social jetlag and metabolic control in non-communicable chronic diseases: a study addressing different obesity statuses. Sci Rep. 2017;7(1):6358.
  • Mokhlesi B, Temple KA, Tjaden AH, et al. Association of self-reported sleep and circadian measures with glycemia in adults with prediabetes or recently diagnosed untreated type 2 diabetes. Diabetes Care. 2019;42(7):1326–1332.
  • Merikanto I, Lahti T, Puolijoki H, et al. Associations of chronotype and sleep with cardiovascular diseases and type 2 diabetes. Chronobiol Int. 2013;30(4):470–477.
  • Stenvers DJ, Scheer F, Schrauwen P, et al. Circadian clocks and insulin resistance. Nat Rev Endocrinol. 2019;15(2):75–89.
  • Gale JE, Cox HI, Qian J, et al. Disruption of circadian rhythms accelerates development of diabetes through pancreatic beta-cell loss and dysfunction. J Biol Rhythms. 2011;26(5):423–433.
  • Scheer FA, Hilton MF, Mantzoros CS, et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106(11):4453–4458.
  • Karamitri A, Jockers R. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol. 2019;15(2):105–125.
  • Peschke E. Melatonin, endocrine pancreas and diabetes. J Pineal Res. 2008;44(1):26–40.
  • Tuomi T, Nagorny CLF, Singh P, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23(6):1067–1077.
  • McMullan CJ, Schernhammer ES, Rimm EB, et al. Melatonin secretion and the incidence of type 2 diabetes. JAMA. 2013;309(13):1388–1396.
  • McMullan CJ, Curhan GC, Schernhammer ES, et al. Association of nurnal melatonin secretion with insulin resistance in nondiabetic young women. Am J Epidemiol. 2013;178(2):231–238.
  • Garfinkel D, Zorin M, Wainstein J, et al. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307–313.
  • Rubio-Sastre P, Scheer FA, Gomez-Abellan P, et al. Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. Sleep. 2014;37(10):1715–1719.
  • Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf). 2001;54(3):339–346.
  • Dubocovich ML. Melatonin receptors: are there multiple subtypes? Trends Pharmacol Sci. 1995;16(2):50–56.
  • Stein RM, Kang HJ, McCorvy JD, et al. Virtual discovery of melatonin receptor ligands to modulate circadian rhythms. Nature. 2020;579(7800):609–614
  • Ramracheya RD, Muller DS, Squires PE, et al. Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res. 2008;44(3):273–279.
  • Blodgett DM, Nowosielska A, Afik S, et al. el observations from Next-Generation RNA sequencing of highly purified human adult and fetal islet cell subsets. Diabetes. 2015;64(9):3172–3181.
  • Bouatia-Naji N, Bonnefond A, Cavalcanti-Proenca C, et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet. 2009;41(1):89–94.
  • Prokopenko I, Langenberg C, Florez JC, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009;41(1):77–81.
  • Dupuis J, Langenberg C, Prokopenko I, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42(2):105–116.
  • Hu C, Jia W. Linking MTNR1B variants to diabetes: the role of circadian rhythms. Diabetes. 2016;65(6):1490–1492.
  • Lane JM, Chang AM, Bjonnes AC, et al. Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes. 2016;65(6):1741–1751.
  • Imam A, Winnebeck EC, Buchholz N, et al. Circadian, sleep and caloric intake phenotyping in type 2 diabetes patients with rare melatonin receptor 2 mutations and controls: a pilot study. Front Physiol. 2020;11:564140.
  • Garaulet M, Lopez-Minguez J, Dashti HS, et al. Interplay of dinner timing and MTNR1B type 2 diabetes risk variant on glucose tolerance and insulin secretion: a randomized crossover trial. Diabetes Care. 2022;45(3):512–519.
  • Mulder H. Melatonin signalling and type 2 diabetes risk: too little, too much or just right? Diabetologia. 2017;60(5):826–829.
  • Florez JC. Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia. 2008;51(7):1100–1110.
  • Dietrich K, Birkmeier S, Schleinitz D, et al. Association and evolutionary studies of the melatonin receptor 1B gene (MTNR1B) in the self-contained population of sorbs from Germany. Diabet Med. 2011;28(11):1373–1380.
  • Ji LD, Xu J, Wu DD, et al. Association of disease-predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations. J Pineal Res. 2010;48(2):133–141.
  • Woelfle MA, Ouyang Y, Phanvijhitsiri K, et al. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr Biol. 2004;14(16):1481–1486.
  • Ouyang Y, Andersson CR, Kondo T, et al. Resonating circadian clocks enhance fitness in cyanobacteria. Proc Natl Acad Sci U S A. 1998;95(15):8660–8664.
  • Fagiani F, Di ino D, Romagnoli A, et al. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther. 2022;7(1):41.
  • Li MD, Xin H, Yuan Y, et al. Circadian Clock-Controlled checkpoints in the pathogenesis of complex disease. Front Genet. 2021;12:721231.
  • Gooley JJ, Chamberlain K, Smith KA, et al. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. J Clin Endocrinol Metab. 2011;96(3):E463–72.
  • Lockley SW, Brainard GC, Czeisler CA. High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J Clin Endocrinol Metab. 2003;88(9):4502–4505.
  • Cipolla-Neto J, Aal FGD. Melatonin as a hormone: new physiological and clinical insights. Endocr Rev. 2018;39(6):990–1028.
  • Riggs W, Jr., Seibert J. Pseudoectopic ureter on prone urogram. Radiology. 1973;106(2):391–392.
  • Huang H, Wang Z, Weng SJ, et al. Neuromodulatory role of melatonin in retinal information processing. Prog Retin Eye Res. 2013;32:64–87.
  • Weaver DR, Stehle JH, Stopa EG, et al. Melatonin receptors in human hypothalamus and pituitary: implications for circadian and reproductive responses to melatonin. J Clin Endocrinol Metab. 1993;76(2):295–301.
  • Reppert SM, Weaver DR, Rivkees SA, et al. Putative melatonin receptors in a human biological clock. Science. 1988;242(4875):78–81.
  • Vriend J, Reiter RJ. Melatonin feedback on clock genes: a theory involving the proteasome. J Pineal Res. 2015;58(1):1–11.
  • Liu J, Clough SJ, Hutchinson AJ, et al. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol. 2016;56:361–383.
  • Gobbi G, Comai S. Sleep well. Untangling the role of melatonin MT1 and MT2 receptors in sleep. J Pineal Res. 2019;66(3):e12544.
  • Zlotos DP, Jockers R, Cecon E, et al. MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 24 2014;57(8):3161–3185.
  • Cipolla-Neto J, Aal FG, Afeche SC, et al. Melatonin, energy metabolism, and obesity: a review. J Pineal Res. 2014;56(4):371–381.
  • Genario R, Cipolla-Neto J, Bueno AA, et al. Melatonin supplementation in the management of obesity and obesity-associated disorders: a review of physiological mechanisms and clinical applications. Pharmacol Res. 2021;163:105254.
  • Garaulet M, Qian J, Florez JC, et al. Melatonin effects on glucose metabolism: time to unlock the controversy. Trends Endocrinol Metab. 2020;31(3):192–204.
  • Reiter RJ, o JC, Tan DX, et al. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res. 2016;61(3):253–278.
  • Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9(1):11–24.
  • Lok R, van Koningsveld MJ, Gordijn MCM, et al. Daytime melatonin and light independently affect human alertness and body temperature. J Pineal Res. 2019;67(1):e12583.
  • Hardeland R. Melatonin and inflammation-story of a double-edged blade. J Pineal Res. 2018;65(4):e12525.
  • Pham L, Baiocchi L, Kennedy L, et al. The interplay between mast cells, pineal gland, and circadian rhythm: links between histamine, melatonin, and inflammatory mediators. J Pineal Res. 2021;70(2):e12699.
  • Ma N, Zhang J, Reiter RJ, et al. Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: a therapeutic target to reduce intestinal inflammation. Med Res Rev. 2020;40(2):606–632.
  • Sato K, Meng F, Francis H, et al. Melatonin and circadian rhythms in liver diseases: functional roles and potential therapies. J Pineal Res. 2020;68(3):e12639.
  • Munmun F, Witt-Enderby PA. Melatonin effects on bone: implications for use as a therapy for managing bone loss. J Pineal Res. 2021;71(1):e12749.
  • Smolensky MH, Hermida RC, Portaluppi F. Circadian mechanisms of 24-hour blood pressure regulation and patterning. Sleep Med Rev. 2017;33:4–16.
  • Ma Q, Reiter RJ, Chen Y. Role of melatonin in controlling angiogenesis under physiological and pathological conditions. Angiogenesis. 2020;23(2):91–104.
  • Opie LH, Lecour S. Melatonin has multiorgan effects. Eur Heart J Cardiovasc Pharmacother. 2016;2(4):258–265.
  • Chen HY, Chen TY, Lee MY, et al. Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood-brain barrier permeability after transient focal cerebral ischemia in mice. J Pineal Res. 2006;41(2):175–182.
  • Kong X, Gao R, Wang Z, et al. Melatonin: a potential therapeutic option for breast cancer. Trends Endocrinol Metab. 2020;31(11):859–871.
  • Su SC, Hsieh MJ, Yang WE, et al. Cancer metastasis: mechanisms of inhibition by melatonin. J Pineal Res. 2017;62(1):1–40.
  • Olcese JM. Melatonin and female reproduction: an expanding universe. Front Endocrinol (Lausanne). 2020;11:85.
  • Vasey C, McBride J, Penta K. Circadian rhythm dysregulation and restoration: the role of melatonin. Nutrients. 2021;13(10):3480.
  • Meyer N, Harvey AG, Lockley SW, et al. Circadian rhythms and disorders of the timing of sleep. Lancet. 2022;400(10357):1061–1078.
  • Nishiyama K, Hirai K. The melatonin agonist ramelteon induces duration-dependent clock gene expression through cAMP signaling in pancreatic INS-1 beta-cells. PLoS One. 2014;9(7):e102073.
  • Kemp DM, Ubeda M, Habener JF. Identification and functional characterization of melatonin mel 1a receptors in pancreatic beta cells: potential role in incretin-mediated cell function by sensitization of cAMP signaling. Mol Cell Endocrinol. 2002;191(2):157–166.
  • Costes S, Boss M, Thomas AP, et al. Activation of melatonin signaling promotes beta-Cell survival and function. Mol Endocrinol. 2015;29(5):682–692.
  • Gil-Lozano M, Wu WK, tchenko A, et al. High-Fat diet and palmitate alter the rhythmic secretion of glucagon-like peptide-1 by the rodent L-cell. Endocrinology. 2016;157(2):586–599.
  • cheva B, Ramsey KM, Buhr ED, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010;466(7306):627–631.
  • Picinato MC, Haber EP, Carpinelli AR, et al. Daily rhythm of glucose-induced insulin secretion by isolated islets from intact and pinealectomized rat. J Pineal Res. 2002;33(3):172–177.
  • Sandu C, Liu T, Malan A, et al. Circadian clocks in rat skin and dermal fibroblasts: differential effects of aging, temperature and melatonin. Cell Mol Life Sci. 2015;72(11):2237–2248.
  • Reinke H, Asher G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol. 2019;20(4):227–241.
  • Stephan FK, Zucker I. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci U S A. 1972;69(6):1583–1586.
  • Czeisler CA, Weitzman E, Moore-Ede MC, et al. Human sleep: its duration and organization depend on its circadian phase. Science. 1980;210(4475):1264–1267.
  • Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257–1263.
  • Herrera-Moro Chao D, Leon-Mercado L, Foppen E, et al. The suprachiasmatic nucleus modulates the sensitivity of arcuate nucleus to hypoglycemia in the male rat. Endocrinology. 2016;157(9):3439–3451.
  • g CM, Melanson EL, Frydendall EJ, et al. Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans. J Physiol. 1 2011;589(Pt 1):235–244.
  • Anothaisintawee T, Reutrakul S, Van Cauter E, et al. Sleep disturbances compared to traditional risk factors for diabetes development: systematic review and meta-analysis. Sleep Med Rev. 2016;30:11–24.
  • Kim TW, Jeong JH, Hong SC. The impact of sleep and circadian disturbance on hormones and metabolism. Int J Endocrinol. 2015;2015:591729. .
  • Moller N, Jorgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009;30(2):152–177.
  • Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab. 2005;90(5):3106–3114.
  • Liu PY, Lawrence-Sidebottom D, Piotrowska K, et al. Clamping cortisol and testosterone mitigates the development of insulin resistance during sleep restriction in men. J Clin Endocrinol Metab. 2021;106(9):e3436–e3448.
  • von Gall C, Weaver DR, Kock M, et al. Melatonin limits transcriptional impact of phosphoCREB in the mouse SCN via the Mel1a receptor. Neuroreport. 000;11(9):1803–1807.
  • Nelson CS, ino JL, Allen CN. Melatonin receptors activate heteromeric G-protein coupled Kir3 channels. Neuroreport. 1996;7(3):717–720.
  • McArthur AJ, Hunt AE, Gillette MU. Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dusk and dawn. Endocrinology. 1997;138(2):627–634.
  • Kandalepas PC, Mitchell JW, Gillette MU. Melatonin signal transduction pathways require E-box-mediated transcription of Per1 and Per2 to reset the SCN clock at dusk. PLoS One. 2016;11(6):e0157824.
  • Pfeffer M, Rauch A, Korf HW, et al. The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon MT2 receptors. Chronobiol Int. 2012;29(4):415–429.
  • Nagy AD, Iwamoto A, Kawai M, et al. Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder. Chronobiol Int. 2015;32(4):447–457.
  • Stumpf I, Muhlbauer E, Peschke E. Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells. J Pineal Res. 2008;45(3):318–327.
  • Peschke E, Muhlbauer E, Musshoff U, et al. Receptor (MT(1)) mediated influence of melatonin on cAMP concentration and insulin secretion of rat insulinoma cells INS-1. J Pineal Res. 2002;33(2):63–71.
  • Peschke E, Bahr I, Muhlbauer E. Experimental and clinical aspects of melatonin and clock genes in diabetes. J Pineal Res. 2015;59(1):1–23. .
  • Ha E, Yim SV, Chung JH, et al. Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. J Pineal Res. 2006;41(1):67–72.
  • Shieh JM, Wu HT, Cheng KC, et al. Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in hepatic cells. J Pineal Res. 2009;47(4):339–344.
  • Altman J, Garay P, Papadimitriou A, et al. Alterations in 22Na fluxes of arterial smooth muscles of spontaneously hypertensive rats. Br J Pharmacol. 1977;59(3):496P.
  • Nogueira TC, Lellis-Santos C, Jesus DS, et al. Absence of melatonin induces night-time hepatic insulin resistance and increased gluconeogenesis due to stimulation of nocturnal unfolded protein response. Endocrinology. 2011;152(4):1253–1263.
  • Peschke E, Schucht H, Muhlbauer E. Long-term enteral administration of melatonin reduces plasma insulin and increases expression of pineal insulin receptors in both wistar and type 2-diabetic Goto-Kakizaki rats. J Pineal Res. 2010;49(4):373–381.
  • Peschke E, Frese T, Chankiewitz E, et al. Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res. 2006;40(2):135–143.
  • Oliveira AC, Andreotti S, Sertie RAL, et al. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats. Life Sci. 2018;199:158–166.
  • Sartori C, Dessen P, Mathieu C, et al. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology. 2009;150(12):5311–5317.
  • Hikichi T, Tateda N, Miura T. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy. Clin Ophthalmol. 2011;5:655–660.
  • Gonciarz M, Bielański W, Partyka R, et al. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin. J Pineal Res. 2013;54(2):154–161.
  • Kadhim HM, Ismail SH, Hussein KI, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res. 2006;41(2):189–193.
  • Sparso T, Bonnefond A, Andersson E, et al. G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans. Diabetes. 2009;58(6):1450–1456.
  • Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010;42(7):579–589.
  • Sabatti C, Service SK, Hartikainen AL, et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet. 2009;41(1):35–46.
  • Ronn T, Wen J, Yang Z, et al. A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals. Diabetologia. 2009;52(5):830–833.
  • Liu C, Wu Y, Li H, et al. MTNR1B rs10830963 is associated with fasting plasma glucose, HbA1C and impaired beta-cell function in chinese hans from shanghai. BMC Med Genet. 2010;11:59.
  • Takeuchi F, Katsuya T, Chakrewarthy S, et al. Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations. Diabetologia. 2010;53(2):299–308.
  • Fujita H, Hara K, Shojima N, et al. Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits. J Hum Genet. 2012;57(12):776–779.
  • Palmer ND, Goodarzi MO, Langefeld CD, et al. Genetic variants associated with quantitative glucose homeostasis traits translate to type 2 diabetes in Mexican Americans: the GUARDIAN (genetics underlying diabetes in hispanics) consortium. Diabetes. 2015;64(5):1853–1866.
  • Ramos E, Chen G, Shriner D, et al. Replication of genome-wide association studies (GWAS) loci for fasting plasma glucose in African-Americans. Diabetologia. 2011;54(4):783–788.
  • Liu CT, Ng MC, Rybin D, et al. Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the candidate gene association resource. Diabetologia. 2012;55(11):2970–2984.
  • Chambers JC, Zhang W, Zabaneh D, et al. Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians. Diabetes. 2009;58(11):2703–2708.
  • Soranzo N, Sanna S, Wheeler E, et al. Common variants at 10 genomic loci influence hemoglobin A(1)(C) levels via glycemic and nonglycemic pathways. Diabetes. 2010;59(12):3229–3239.
  • Kraja AT, Vaidya D, Pankow JS, et al. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium. Diabetes. 2011;60(4):1329–1339.
  • Kim YJ, Go MJ, Hu C, MAGIC consortium, et al. Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits. Nat Genet. 2011;43(10):990–995.
  • Kettunen J, Tukiainen T, Sarin AP, et al. Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nat Genet. 2012;44(3):269–276.
  • Rasmussen-Torvik LJ, Guo X, Bowden DW, et al. Fasting glucose GWAS candidate region analysis across ethnic groups in the multiethnic study of atherosclerosis (MESA). Genet Epidemiol. 2012;36(4):384–391.
  • Manning AK, Hivert MF, Scott RA, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012;44(6):659–669.
  • Comuzzie AG, Cole SA, Laston SL, et al. Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PLoS One. 2012;7(12):e51954.
  • Kwak SH, Kim SH, Cho YM, et al. A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes. . 2012;61(2):531–541.
  • Kristiansson K, Perola M, Tikkanen E, et al. Genome-wide screen for metabolic syndrome susceptibility loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ Cardiovasc Genet. 2012;5(2):242–249.
  • Morris CJ, Yang JN, Scheer F. The impact of the circadian timing system on cardiovascular and metabolic function. Prog Brain Res. 2012;199:337–358.
  • Go MJ, Hwang JY, Kim YJ, et al. New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the korean population. J Hum Genet. 2013;58(6):362–365.
  • Hayes MG, Urbanek M, Hivert MF, HAPO Study Cooperative Research Group, et al. Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes. 2013;62(9):3282–3291.
  • Prokopenko I, Poon W, Magi R, et al. A Central role for GRB10 in regulation of islet function in man. PLoS Genet. 2014;10(4):e1004235.
  • Maha A, Go MJ, Zhang W. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet. 2014;46(3):234–244.
  • Wessel J, Chu AY, Willems SM, et al. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun. 2015;6:5897.
  • Kettunen J, Demirkan A, Wurtz P, et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals el systemic effects of LPA. Nat Commun. 2016;7:11122.
  • Horikoshi M, Beaumont RN, Day FR, et al. Genome-wide associations for birth weight and correlations with adult disease. Nature. 2016;538(7624):248–252.
  • Wood AR, Jonsson A, Jackson AU, et al. A genome-wide association study of IVGTT-based measures of first-phase insulin secretion refines the underlying physiology of type 2 diabetes variants. Diabetes. 2017;66(8):2296–2309.
  • Wheeler E, Leong A, Liu CT, et al. Impact of common genetic determinants of hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis. PLoS Med. 2017;14(9):e1002383.
  • Zhao W, Rasheed A, Tikkanen E, Michigan Biobank, et al. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease. Nat Genet. 2017;49(10):1450–1457.
  • Qi Q, Stilp AM, Sofer T, et al. Genetics of type 2 diabetes in U.S. Hispanic/latino individuals: results from the hispanic community health study/study of latinos (HCHS/SOL). Diabetes. . 2017;66(5):1419–1425.
  • Beaumont RN, Warrington NM, Cavadino A, et al. Genome-wide association study of offspring birth weight in 86 577 women identifies five el loci and highlights maternal genetic effects that are independent of fetal genetics. Hum Mol Genet. 2018;27(4):742–756.
  • Kanai M, Akiyama M, Takahashi A, et al. Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases. Nat Genet. 2018;50(3):390–400.
  • Wu B, Pankow JS. Fast and accurate genome-wide association test of multiple quantitative traits. Comput Math Methods Med. 2018;2018:2564531.
  • Loomis SJ, Li M, uthur NM, et al. Genome-wide association study of serum fructosamine and glycated albumin in adults without diagnosed diabetes: results from the atherosclerosis risk in communities study. Diabetes. 2018;67(8):1684–1696.
  • Kichaev G, Bhatia G, Loh PR, et al. Leveraging polygenic functional enrichment to improve GWAS power. Am J Hum Genet. 2019;104(1):65–75.
  • Keaton JM, Gao C, Guan M, et al. Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a el type 2 diabetes susceptibility gene in african americans. Genet Epidemiol. 2018;42(6):559–570.
  • Bonas-Guarch S, Guindo-tinez M, Miguel-Escalada I, et al. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. Nat Commun. 22 2018;9(1):321.
  • van Zuydam NR, Ahlqvist E, Sandholm N, et al. A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes. Diabetes. . 2018;67(7):1414–1427.
  • Xue A, Wu Y, Zhu Z, et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018;9(1):2941.
  • Maha A, Taliun D, Thurner M, et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018;50(11):1505–1513.
  • Masotti M, Guo B, Wu B. Pleiotropy informed adaptive association test of multiple traits using genome-wide association study sumy data. Biometrics. 2019;75(4):1076–1085.
  • Warrington NM, Beaumont RN, Horikoshi M, et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet. 2019;51(5):804–814.
  • Wojcik GL, Graff M, Nishimura KK, et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature. 2019;570(7762):514–518.
  • Gallois A, Mefford J, Ko A, et al. A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context. Nat Commun. 2019;10(1):4788.
  • Zhu Z, Guo Y, Shi H, et al. Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK biobank. J Allergy Clin Immunol. 2020;145(2):537–549.
  • ienne H, Lechat P, Guillemot V, et al. JASS: command line and web interface for the joint analysis of GWAS results. NAR Genom Bioinform. 2020;2(1):lqaa003.
  • Oh SW, Lee JE, Shin E, et al. Genome-wide association study of metabolic syndrome in korean populations. PLoS One. 2020;15(1):e0227357.
  • Vujkovic M, Keaton JM, Lynch JA, et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat Genet. 2020;52(7):680–691.
  • Spracklen CN, Horikoshi M, Kim YJ, et al. Identification of type 2 diabetes loci in 433,540 east asian individuals. Nature. 2020;582(7811):240–245.
  • Lagou V, Magi R, Hottenga JJ, et al. Sex-dimorphic genetic effects and el loci for fasting glucose and insulin variability. Nat Commun. J2021;12(1):24.
  • Sinnott-Armstrong N, Tanigawa Y, A D, et al. Genetics of 35 blood and urine biokers in the UK biobank. Nat Genet. 2021;53(2):185–194.
  • Chung RH, Chiu YF, Wang WC, et al. Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose. Diabetologia. 2021;64(7):1613–1625.
  • Chen J, Spracklen CN, enne G, et al. The trans-ancestral genomic architecture of glycemic traits. Nat Genet. 2021;53(6):840–860.
  • Sakaue S, Kanai M, Tanigawa Y, et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53(10):1415–1424.
  • Li-Gao R, Hughes DA, van Klinken JB, et al. Genetic studies of metabolomics change after a liquid meal illuminate el pathways for glucose and lipid metabolism. Diabetes. 2021;70(12):2932–2946.
  • Downie CG, Dimos SF, Bien SA, et al. Multi-ethnic GWAS and fine-mapping of glycaemic traits identify el loci in the PAGE study. Diabetologia. 2022;65(3):477–489.
  • DiCorpo D, Gaynor SM, Russell EM, et al. Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program. Commun Biol. 2022;5(1):756.
  • Tchio C, Musani SK, Quarshie A, et al. Association between MTNR1B polymorphisms and obesity in African American: findings from the jackson heart study. BMC Med Genomics. 2021;14(1):136.
  • Song JF, Zhang J, Zhang MZ, et al. Evaluation of the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating type 2 diabetes among chinese han patients. BMC Med Genomics. 2021;14(1):156.
  • Tan X, Benedict C. Does the common type 2 Diabetes-Susceptibility variant in the MTNR1B gene matter for glycemic control among patients on antidiabetic pharmacotherapy? Clin Proc. 2021;96(5):1372–1374.
  • Garaulet M, Gomez-Abellan P, Rubio-Sastre P, et al. Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans. Metabolism. 2015;64(12):1650–1657.
  • Kampmann U, Lauritzen ES, Grarup N, et al. Acute metabolic effects of melatonin – a randomized crossover study in healthy young men. J Pineal Res. 2021;70(2):e12706.
  • Cherrington AD. Banting lecture 1997. Control of glucose uptake and release by the liver in vivo. Diabetes. 1999;48(5):1198–1214.
  • Magnusson I, Rothman DL, Katz LD, et al. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest. 1992;90(4):1323–1327.
  • Vangipurapu J, Stancakova A, Pihlajamaki J, et al. Association of indices of liver and adipocyte insulin resistance with 19 confirmed susceptibility loci for type 2 diabetes in 6,733 non-diabetic finnish men. Diabetologia. 2011;54(3):563–571.
  • Staiger H, Machicao F, Schafer SA, et al. Polymorphisms within the el type 2 diabetes risk locus MTNR1B determine beta-cell function. PLoS One. 2008;3(12):e3962.
  • Lyssenko V, Nagorny CL, Erdos MR, et al. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2009;41(1):82–88.
  • van de Bunt M, Manning Fox JE, Dai X, et al. Transcript expression data from human islets links regulatory signals from Genome-Wide association studies for type 2 diabetes and glycemic traits to their downstream effectors. PLoS Genet. 2015;11(12):e1005694.
  • Li Y, Wu H, Liu N, et al. Melatonin exerts an inhibitory effect on insulin gene transcription via MTNR1B and the downstream Raf1/ERK signaling pathway. Int J Mol Med. 2018;41(2):955–961.
  • Gaulton KJ, Ferreira T, Lee Y, et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet. 2015;47(12):1415–1425.
  • Bonnefond A, Clement N, Fawcett K, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44(3):297–301.
  • Zibolka J, Bazwinsky-Wutschke I, Muhlbauer E, et al. Distribution and density of melatonin receptors in human main pancreatic islet cell types. J Pineal Res. 2018;65(1):e12480.
  • Bahr I, Muhlbauer E, Schucht H, et al. Melatonin stimulates glucagon secretion in vitro and in vivo. J Pineal Res. 2011;50(3):336–344.
  • Zibolka J, Muhlbauer E, Peschke E. Melatonin influences somatostatin secretion from human pancreatic Delta-cells via MT1 and MT2 receptors. J Pineal Res. 2015;58(2):198–209.
  • Jonsson A, Ladenvall C, Ahluwalia TS, et al. Effects of common genetic variants associated with type 2 diabetes and glycemic traits on alpha- and beta-cell function and insulin action in humans. Diabetes. . 2013;62(8):2978–2983.
  • You H, Hu J, Liu Y, et al. Risk of type 2 diabetes mellitus after gestational diabetes mellitus: a systematic review & meta-analysis. Indian J Med Res. 2021;154(1):62–77.
  • Pervjakova N, Moen GH, Borges MC, et al. Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes. Hum Mol Genet. 2022;31(19):3377–3391.
  • Powe CE, Kwak SH. Genetic studies of gestational diabetes and glucose metabolism in pregnancy. Curr Diab Rep. 2020;20(12):69.
  • Liao S, Liu Y, Chen X, et al. The impact of genetic variants for different physiological characterization of type 2 diabetes loci on gestational insulin signaling in nondiabetic pregnant chinese women. Reprod Sci. 2015;22(11):1421–1428.
  • Vlassi M, Gazouli M, Paltoglou G, et al. The rs10830963 variant of melatonin receptor MTNR1B is associated with increased risk for gestational diabetes mellitus in a Greek population. Hormones (Athens). - 2012;11(1):70–76.
  • Kim JY, Cheong HS, Park BL, et al. Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus. BMC Med Genet. 10 2011;12:82.
  • Huopio H, Cederberg H, Vangipurapu J, et al. Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes. Eur J Endocrinol. 2013;169(3):291–297.
  • Ding M, Chavarro J, Olsen S, et al. Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations. Diabetologia. 2018;61(8):1758–1768.
  • Grotenfelt NE, Wasenius NS, Rono K, et al. Interaction between rs10830963 polymorphism in MTNR1B and lifestyle intervention on occurrence of gestational diabetes. Diabetologia. 2016;59(8):1655–1658.
  • van Poppel MNM, Corcoy R, Hill D, DALI Core Investigator Group, et al. Interaction between rs10830962 polymorphism in MTNR1B and lifestyle intervention on maternal and neonatal outcomes: secondary analyses of the DALI lifestyle randomized controlled trial. Am J Clin Nutr. 9 2022;115(2):388–396.
  • Liang Z, Liu H, Wang L, et al. Maternal MTNR1B genotype, maternal gestational weight gain, and childhood obesity. Am J Clin Nutr. 1 2020;111(2):360–368.
  • Nisa H, Qi KHT, Leng J, et al. The circadian rhythm-related MTNR1B genotype, gestational weight gain, and postpartum glycemic changes. J Clin Endocrinol Metab. 2018;103(6):2284–2290. .
  • Firneisz G, Rosta K, Rigo J, et al. Identification and potential clinical utility of the MTNR1B rs10830963 core gene variant associated to endophenotypes in gestational diabetes mellitus. Front Genet. 2020;11:332.
  • Zhang C, Bao W, Rong Y, et al. Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update. - 2013;19(4):376–390.
  • Wu L, Cui L, Tam WH, et al. Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis. Sci Rep. 29 2016;6:30539.
  • Vejrazkova D, Lukasova P, Vankova M, et al. MTNR1B genetic variability is associated with gestational diabetes in czech women. Int J Endocrinol. 2014;2014:508923.
  • Alharbi KK, Al-Sulaiman AM, Shedaid KMB, et al. MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center. Ann Saudi Med. 2019;39(5):309–318.
  • Zhang Y, Sun CM, Hu XQ, et al. Relationship between melatonin receptor 1B and insulin receptor substrate 1 polymorphisms with gestational diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2014;4:6113.
  • Rosta K, Al-Aissa Z, Hadarits O, et al. Association study with 77 SNPs confirms the robust role for the rs10830963/G of MTNR1B variant and identifies two el associations in gestational diabetes mellitus development. PLoS One. 2017;12(1):e0169781.
  • Nakamura Y, Tamura H, Kashida S, et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res. 2001;30(1):29–33.
  • Li C, Zhou Y, Qiao B, et al. Association between a melatonin receptor 1B genetic polymorphism and its protein expression in gestational diabetes mellitus. Reprod Sci. 2019;26(10):1382–1388.
  • Holzapfel C, Siegrist M, Rank M, et al. Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS. Eur J Endocrinol. 2011;164(2):205–212.
  • de Luis Roman DA, Primo D, Aller R, et al. Association of the rs10830963 polymorphism in MTNR1B with fasting glucose, serum adipokine levels and components of metabolic syndrome in adult obese subjects. rs10830963 en MTNR1B con los niveles de glucosa en ayunas, de adipocitoquinas y componentes del sindrome metabolico en sujetos obesos adultos. Nutr Hosp. 2019;36(1):60–65. Asociacion del polimorfi smo
  • Zheng C, Dalla Man C, Cobelli C, et al. A common variant in the MTNR1b gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity. Obesity. 2015;23(5):1022–1029.
  • Reinehr T, Scherag A, Wang HJ, et al. Relationship between MTNR1B (melatonin receptor 1B gene) polymorphism rs10830963 and glucose levels in overweight children and adolescents. Pediatr Diabetes. 2011;12(4 Pt 2):435–441.
  • Firneisz G, Rosta K, Al-Aissa Z, et al. The MTNR1B rs10830963 variant in interaction with Pre-Pregnancy BMI is a pharmacogenetic ker for the initiation of antenatal insulin therapy in gestational diabetes mellitus. Int J Mol Sci. 2018;19(12):3734.
  • Jensen AC, Barker A, Kui M, et al. Associations of common genetic variants with age-related changes in fasting and postload glucose: evidence from 18 years of follow-up of the whitehall II cohort. Diabetes. 2011;60(5):1617–1623.
  • Walford GA, Green T, Neale B, et al. Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. Diabetologia. 2012;55(2):331–339.
  • Vejrazkova D, Vankova M, Vcelak J, et al. The rs10830963 polymorphism of the MTNR1B gene: association with abnormal glucose, insulin and C-peptide kinetics. Front Endocrinol (Lausanne). 2022;13:868364.
  • Linder K, Wagner R, Hatziagelaki E, et al. Allele summation of diabetes risk genes predicts impaired glucose tolerance in female and obese individuals. PLoS One. 2012;7(6):e38224.
  • Stancakova A, Kuulasmaa T, Paananen J, et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009;58(9):2129–2136.
  • Winkler C, Raab J, Grallert H, et al. Lack of association of type 2 diabetes susceptibility genotypes and body weight on the development of islet autoimmunity and type 1 diabetes. PLoS One. 2012;7(4):e35410.
  • Andersen MK, Sterner M, Forsen T, et al. Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes. Diabetologia. 2014;57(9):1859–1868.
  • Ahlqvist E, Storm P, Karajamaki A, et al. el subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;6(5):361–369.
  • Neel JV, JV. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress”?. Am J Hum Genet. 1962;14(4):353–362.
  • Ayub Q, Moutsianas L, Chen Y, et al. Revisiting the thrifty gene hypothesis via 65 loci associated with susceptibility to type 2 diabetes. Am J Hum Genet. 6 2014;94(2):176–185.
  • Li H, Durbin R. Inference of human population history from individual whole-genome sequences. Nature. 2011;475(7357):493–496.
  • Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320–323.
  • Helgason A, Palsson S, Thorleifsson G, et al. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet. 2007;39(2):218–225.
  • Southam L, Soranzo N, Montgomery SB, et al. Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants? Diabetologia. 2009;52(9):1846–1851.
  • Klimentidis YC, Abrams M, Wang J, et al. Natural selection at genomic regions associated with obesity and type-2 diabetes: east asians and Sub-Saharan africans exhibit high levels of differentiation at type-2 diabetes regions. Hum Genet. 2011;129(4):407–418.
  • Chen R, Corona E, Sikora M, et al. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. PLoS Genet. 2012;8(4):e1002621.
  • Gibbons A. 12th international congress of human genetics. Diabetes genes line out of Africa. Science. 2011;334(6056):583.
  • Neel JV. The "thrifty genotype" in 1998. Nutr Rev. 1999;57(5 Pt 2):S2–S9.
  • Reppert SM, Godson C, Mahle CD, et al. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A. 995;92(19):8734–8738.
  • Mars G, Nourizadeh-Lillabadi R, Weltzien FA. New insights into the evolutionary history of melatonin receptors in vertebrates, with particular focus on teleosts. Front Endocrinol. 2020;11:538196.
  • Yoshiuchi I. Analysis of evolution and ethnic diversity at glucose-associated SNPs of circadian clock-related loci with cryptochrome 1, cryptochrome 2, and melatonin receptor 1b. Biochem Genet. 2021;59(5):1173–1184.
  • De Oliveira JW. [An undetermined form of chagas’ disease: medico-occupational implications]. arq bras cardiol. Forma Indeterminada da Doenca de Chagas. Implicacaoes Medico-Trabalhistas. 1990;54(2):89–91.