Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go?

Current Diabetes Reports

Volumn 17, Issue 12, 2017, Pages

  Bonnefond, Amélie ^a   Froguel, Philippe ^a,b  

^a UNIV LILLE   (France)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Circadian rhythm; Clock; Expression quantitative trait loci (eQTL); Genome wide association study (GWAS); Insulin secretion; Melatonin; MTNR1B; Pancreatic beta cell; Rare genetic variant

Indexed keywords

GLUCOSE; INSULIN; MELATONIN; MELATONIN 1 RECEPTOR; MELATONIN 1B RECEPTOR; MESSENGER RNA; TRANSCRIPTOME; UNCLASSIFIED DRUG; MELATONIN 2 RECEPTOR;

CIRCADIAN RHYTHM; DISEASE MODEL; DNA SEQUENCE; ETHNIC DIFFERENCE; GENE; GENE FREQUENCY; GENE LOCATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; GENOTYPE; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; HUMAN; INSULIN RELEASE; LOSS OF FUNCTION MUTATION; MTNR1B GENE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PATHOPHYSIOLOGY; QUANTITATIVE TRAIT LOCUS; REVIEW; RNA SEQUENCE; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; ANIMAL; BLOOD; GENETICS; METABOLISM; SECRETION (PROCESS);

ANIMALS; CIRCADIAN RHYTHM; DIABETES MELLITUS, TYPE 2; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INSULIN; MELATONIN; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTOR, MELATONIN, MT2;

EID: 85032198351     PISSN: 15344827     EISSN: 15390829     Source Type: Journal    
DOI: 10.1007/s11892-017-0957-1     Document Type: Review

References (59)

1. Association AD. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40:S11–24.
2. Vftter K. Diabetes mellitus. WHO technical report series 727. 113 Seiten. World Health Organization, Geneva 1985. Preis: 9.00 Sw. fr. Food Nahr. 1986;30:700.
3. Bonnefond A, Froguel P. Rare and common genetic events in type 2 diabetes: what should biologists know? Cell Metab. 2015;21:357–68.
4. Wheeler E, Marenne G, Barroso I. Genetic aetiology of glycaemic traits—approaches and insights. Hum Mol Genet. [Internet]. [cited 2017 Jul 25]; Available from: https://academic.oup.com/hmg/article/doi/10.1093/hmg/ddx293/4016580/Genetic-aetiology-of-glycaemic-traits-approaches
5. Mulder H. Melatonin signalling and type 2 diabetes risk: too little, too much or just right? Diabetologia. 2017;60:826-829.
6. Bonnefond A, Froguel P. The case for too little melatonin signalling in increased diabetes risk. Diabetologia. 2017;60:823-825.
7. Bonnefond A, Karamitri A, Jockers R, Froguel P. The difficult journey from genome-wide association studies to pathophysiology: the melatonin receptor 1B (MT2) paradigm. Cell Metab. 2016;24:345–7.
8. • Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, Sparsø T, Holmkvist J, Marchand M, et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet. 2009;41:89–94. Among the three publications that primarily identify the effect of MTNR1B locus on the variation of fasting glucose or insulin-secretion-related traits and on type 2 diabetes risk, through hypothesis-free genome-wide association studies.
9. • Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009;41:77–81. Among the three publications that primarily identify the effect of MTNR1B locus on the variation of fasting glucose or insulin-secretion-related traits and on type 2 diabetes risk, through hypothesis-free genome-wide association studies.
10. Sparsø T, Bonnefond A, Andersson E, Bouatia-Naji N, Holmkvist J, Wegner L, 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;58:1450–6.
11. Rönn T, Wen J, Yang Z, Lu B, Du Y, Groop L, 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;52:830–3.
12. Chambers JC, Zhang W, Zabaneh D, Sehmi J, Jain P, McCarthy MI, 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;58:2703–8.
13. Liu C, Wu Y, Li H, Qi Q, Langenberg C, Loos RJF, 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.
14. Takeuchi F, Katsuya T, Chakrewarthy S, Yamamoto K, Fujioka A, Serizawa M, et al. Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations. Diabetologia. 2010;53:299–308.
15. Kan MY, Zhou DZ, Zhang D, Zhang Z, Chen Z, Yang YF, et al. Two susceptible diabetogenic variants near/in MTNR1B are associated with fasting plasma glucose in a Han Chinese cohort. Diabet Med J Br Diabet Assoc. 2010;27:598–602.
16. Ramos E, Chen G, Shriner D, Doumatey A, Gerry NP, Herbert A, et al. Replication of genome-wide association studies (GWAS) loci for fasting plasma glucose in African-Americans. Diabetologia. 2011;54:783–8.
17. Kim YJ, Go MJ, Hu C, Hong CB, Kim YK, Lee JY, et al. Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. Nat Genet. 2011;43:990–5.
18. Rasmussen-Torvik LJ, Guo X, Bowden DW, Bertoni AG, Sale MM, Yao J, et al. Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). Genet Epidemiol. 2012;36:384–91.
19. • Lyssenko V, Nagorny CLF, Erdos MR, Wierup N, Jonsson A, Spégel P, et al. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2009;41:82–8. Among the three publications that primarily identify the effect of MTNR1B locus on the variation of fasting glucose or insulin-secretion-related traits and on type 2 diabetes risk, through hypothesis-free genome-wide association studies.
20. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42:105–16.
21. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010;42:579–89.
22. Ling Y, Li X, Gu Q, Chen H, Lu D, Gao XA. Common polymorphism rs3781637 in MTNR1B is associated with type 2 diabetes and lipids levels in Han Chinese individuals. Cardiovasc Diabetol. 2011;10:27.
23. Ohshige T, Iwata M, Omori S, Tanaka Y, Hirose H, Kaku K, et al. Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. PLoS One. 2011;6:e26911.
24. Zhao Q, Xiao J, He J, Zhang X, Hong J, Kong X, et al. Cross-sectional and longitudinal replication analyses of genome-wide association loci of type 2 diabetes in Han Chinese. PLoS One. 2014;9:e91790.
25. Prokopenko I, Poon W, Mägi R, Prasad BR, Salehi SA, Almgren P, et al. A central role for GRB10 in regulation of islet function in man. PLoS Genet. 2014;10:e1004235.
26. Wood AR, Jonsson A, Jackson AU, Wang N, van Leewen N, Palmer ND, 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;66:2296–309.
27. Pandi-Perumal SR, Srinivasan V, Maestroni GJM, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: nature’s most versatile biological signal? FEBS J. 2006;273:2813–38.
28. Clarke T, Black L, Stussman B, Barnes P, Nahin R. Use of complementary health approaches among children aged 4–17 years in the United States: National Health Interview Survey, 2007–2012. National Health Statistics Reports; No 78. Natl. Cent. Health Stat.—CDC. 2015.
29. Clarke T, Black L, Stussman B, Barnes P, Nahin R. Trends in the use of complementary health approaches among adults: United States, 2002–2012. National Health Statistics Reports; No 79. Natl Cent Health Stat.—CDC. 2015.
30. Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000;343:1070–7.
31. Yu H, Dickson EJ, Jung S-R, Koh D-S, Hille B. High membrane permeability for melatonin. J Gen Physiol. 2016;147:63–76.
32. Kim HJ, Kim HJ, Bae M-K, Kim Y-D. Suppression of osteoclastogenesis by melatonin: a melatonin receptor-independent action. Int J Mol Sci. [Internet]. 2017;18. Available from: http://www.mdpi.com/1422-0067/18/6/1142
33. Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. A review of melatonin, its receptors and drugs. Eurasian. J Med. 2016;48:135–41.
34. Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJM, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85:335–53.
35. Calvo JR, González-Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: a review. J Pineal Res. 2013;55:103–20.
36. Feng NY, Bass AH. “Singing” fish rely on circadian rhythm and melatonin for the timing of nocturnal courtship vocalization. Curr Biol. 2016;26:2681–9.
37. Tuomi T, Nagorny CLF, Singh P, Bennet H, Yu Q, Alenkvist I, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23:1067–77.
38. Bazwinsky-Wutschke I, Bieseke L, Mühlbauer E, Peschke E. Influence of melatonin receptor signalling on parameters involved in blood glucose regulation. J Pineal Res. 2014;56:82–96.
39. Costes S, Boss M, Thomas AP, Matveyenko AV. Activation of melatonin signaling promotes β-cell survival and function. Mol Endocrinol. 2015;29:682–92.
40. Thomas AP, Hoang J, Vongbunyong K, Nguyen A, Rakshit K, Matveyenko AV. Administration of melatonin and metformin prevents deleterious effects of circadian disruption and obesity in male rats. Endocrinology. 2016;157:4720–31.
41. Zhou J, Zhang J, Luo X, Li M, Yue Y, Laudon M, et al. Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axis in rats. Eur J Pharmacol. [Internet]. 2017 [cited 2017 Jul 14]; Available from: http://linkinghub.elsevier.com/retrieve/pii/S0014299917304466
42. Rubio-Sastre P, Scheer FAJL, Gómez-Abellán P, Madrid JA, Garaulet M. Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. Sleep. 2014;37:1715–9.
43. McMullan CJ, Schernhammer ES, Rimm EB, FB H, Forman JP. Melatonin secretion and the incidence of type 2 diabetes. JAMA. J Am Med Assoc. 2013;309:1388–96.
44. Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M, et al. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes. [Internet]. 2017;db161253. Available from: http://diabetes.diabetesjournals.org/content/early/2017/05/25/db16-1253.long
45. Franks PW, McCarthy MI. Exposing the exposures responsible for type 2 diabetes and obesity. Science. 2016;354:69–73.
46. Edwards SL, Beesley J, French JD, Dunning AM. Beyond GWASs: illuminating the dark road from association to function. Am J Hum Genet. 2013;93:779–97.
47. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485:376–80.
48. Fadista J, Vikman P, Laakso EO, Mollet IG, Esguerra JL, Taneera J, et al. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Proc Natl Acad Sci. 2014;111:13924–9.
49. van de Bunt M, Manning Fox JE, Dai X, Barrett A, Grey C, Li L, 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:e1005694.
50. Bonnefond A, Clément N, Fawcett K, Yengo L, Vaillant E, Guillaume J-L, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44:297–301.
51. Segerstolpe Å, Palasantza A, Eliasson P, Andersson E-M, Andréasson A-C, Sun X, et al. Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes. Cell Metab. 2016;24:593–607.
52. Thomsen SK, Ceroni A, van de Bunt M, Burrows C, Barrett A, Scharfmann R, et al. Systematic functional characterization of candidate causal genes for type 2 diabetes risk variants. Diabetes. 2016;65:3805–11.
53. Williams EG, Wu Y, Jha P, Dubuis S, Blattmann P, Argmann CA, et al. Systems proteomics of liver mitochondria function. Science. 2016;352:aad0189.
54. Battle A, Khan Z, Wang SH, Mitrano A, Ford MJ, Pritchard JK, et al. Impact of regulatory variation from RNA to protein. Science. 2015;347:664–7.
55. Shu L, Matveyenko AV, Kerr-Conte J, Cho J-H, McIntosh CHS, Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet. 2009;18:2388–99.
56. Gaulton KJ, Ferreira T, Lee Y, Raimondo A, Mägi R, Reschen ME, et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet. 2015;47:1415–25.
57. Pasquali L, Gaulton KJ, Rodríguez-Seguí SA, Mularoni L, Miguel-Escalada I, Akerman I, et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat Genet. 2014;46:136–43.
58. Lane JM, Chang A-M, Bjonnes AC, Aeschbach D, Anderson C, Cade BE, et al. Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes. 2016;65:1741–51.
59. Bansal V, Gassenhuber J, Phillips T, Oliviera G, Villarasa N, Tisch R, et al. Targeted sequencing of genes associated with type 2 diabetes in 6800 individuals. Am Soc Hum Genet—Meet Abstr. 2014;760S. Available from: http://www.ashg.org/2014meeting/abstracts/fulltext/f140122299.htm