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Current Diabetes Reports

Erschienen in:

01.12.2012 | Genetics (T Frayling, Section Editor)

Tired of Diabetes Genetics? Circadian Rhythms and Diabetes: The MTNR1B Story?

verfasst von: Cecilia Nagorny, Valeriya Lyssenko

Erschienen in: Current Diabetes Reports | Ausgabe 6/2012

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Abstract

Circadian rhythms are ubiquitous in biological systems and regulate metabolic processes throughout the body. Misalliance of these circadian rhythms and the systems they regulate has a profound impact on hormone levels and increases risk of developing metabolic diseases. Melatonin, a hormone secreted by the pineal gland, is one of the major signaling molecules used by the master circadian oscillator to entrain downstream circadian rhythms. Several recent genetic studies have pointed out that a common variant in the gene that encodes the melatonin receptor 2 (MTNR1B) is associated with impaired glucose homeostasis, reduced insulin secretion, and an increased risk of developing type 2 diabetes. Here, we try to review the role of this receptor and its signaling pathways in respect to glucose homeostasis and development of the disease.

Green CB, Takahashi JS, Bass J. The meter of metabolism. Cell. 2008;134(5):728–42.PubMedCrossRef

Lamia KA, Evans RM. Metabolism: tick, tock, a beta-cell clock. Nature. 2010;466(7306):571–2.PubMedCrossRef

Stamenkovic JA, Olsson AH, Nagorny CL, Malmgren S, Dekker-Nitert M, Ling C, et al. Regulation of core clock genes in human islets. Metabolism. 2012;61(7):978–85.PubMedCrossRef

Hardeland R, Madrid JA, Tan DX, Reiter RJ. Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling. J Pineal Res. 2012;52(2):139–66.PubMedCrossRef

Shea SA. Obesity and pharmacologic control of the body clock. N Eng J Med. 2012;367(2):175–8.CrossRef

Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106(11):4453–8.PubMedCrossRef

Simonneaux V, Ribelayga C. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev. 2003;55(2):325–95.PubMedCrossRef

Boutin JA, Audinot V, Ferry G, Delagrange P. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005;26(8):412–9.PubMedCrossRef

Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005;27(2):119–30.PubMedCrossRef

10.

Kvetnoy I, Sandvik AK, Waldum HL. The diffuse neuroendocrine system and extrapineal melatonin. J Mol Endocrinol. 1997;18(1):1–3.PubMedCrossRef

11.

Peschke E. Melatonin, endocrine pancreas and diabetes. J Pineal Res. 2008;44(1):26–40.PubMed

12.

Dubocovich ML, Markowska M. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine. 2005;27(2):101–10.PubMedCrossRef

13.

Arendt J. Melatonin and the mammalian pineal gland. London: Chapman and Hall; 1994.

14.

Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: nature’s most versatile biological signal? FEBS J. 2006;273(13):2813–38.PubMedCrossRef

15.

Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S. Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythms. 1997;12(6):604–17.PubMedCrossRef

16.

Arendt J. Does melatonin improve sleep? Efficacy of melatonin. BMJ. 2006;332(7540):550.PubMedCrossRef

17.

Zhdanova IV, Wurtman RJ. Efficacy of melatonin as a sleep-promoting agent. J Biol Rhythms. 1997;12(6):644–50.PubMedCrossRef

18.

Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP, Dubocovich ML, et al. MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther. 2002;302(3):1295–302.PubMedCrossRef

19.

Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971;33(1):14–22.PubMedCrossRef

20.

Brydon L, Petit L, Delagrange P, Strosberg AD, Jockers R. Functional expression of MT2 (Mel1b) melatonin receptors in human PAZ6 adipocytes. Endocrinology. 2001;142(10):4264–71.PubMedCrossRef

21.

Ha E, Yim SV, Chung JH, Yoon KS, Kang I, Cho YH, 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.PubMedCrossRef

22.

Poon AM, Choy EH, Pang SF. Modulation of blood glucose by melatonin: a direct action on melatonin receptors in mouse hepatocytes. Biol Signals Recept. 2001;10(6):367–79.PubMedCrossRef

23.

Peschke E, Frese T, Chankiewitz E, Peschke D, Preiss U, Schneyer U, 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):135–43.PubMedCrossRef

24.

Bailey CJ, Atkins TW, Matty AJ. Melatonin inhibition of insulin secretion in the rat and mouse. Horm Res. 1974;5(1):21–8.PubMedCrossRef

25.

Ramracheya RD, Muller DS, Squires PE, Brereton H, Sugden D, Huang GC, et al. Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res. 2008;44(3):273–9.PubMedCrossRef

26.

Chen CQ, Fichna J, Bashashati M, Li YY, Storr M. Distribution, function and physiological role of melatonin in the lower gut. World J Gastroenterol: WJG. 2011;17(34):3888–98.PubMedCrossRef

27.

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):157–66.PubMedCrossRef

28.

von Gall C, Stehle JH, Weaver DR. Mammalian melatonin receptors: molecular biology and signal transduction. Cell Tissue Res. 2002;309(1):151–62.CrossRef

29.

Mazzucchelli C, Pannacci M, Nonno R, Lucini V, Fraschini F, Stankov BM. The melatonin receptor in the human brain: cloning experiments and distribution studies. Brain Res Mol Brain Res. 1996;39(1–2):117–26.PubMedCrossRef

30.

Al-Ghoul WM, Herman MD, Dubocovich ML. Melatonin receptor subtype expression in human cerebellum. Neuroreport. 1998;9(18):4063–8.PubMedCrossRef

31.

Reppert SM, Weaver DR, Ebisawa T. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron. 1994;13(5):1177–85.PubMedCrossRef

32.

Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335–53.PubMedCrossRef

33.

Poirel VJ, Cailotto C, Streicher D, Pevet P, Masson-Pevet M, Gauer F. MT1 melatonin receptor mRNA tissular localization by PCR amplification. Neuro Endocrinol Lett. 2003;24(1–2):33–8.PubMed

34.

• Nagorny CL, Sathanoori R, Voss U, Mulder H, Wierup N. Distribution of melatonin receptors in murine pancreatic islets. J Pineal Res. 2011;50(4):412–7. This study provides evidence for the localization of melatonin receptors in mouse islets on the protein level, not only their expression, but also their cellular localization in the islet. It demonstrates that MT1 is expressed in α-cells while MT2 is located to the β-cells. These findings help to understand the complex machinery underlying melatonin’s role in the regulation of islet function.PubMedCrossRef

35.

Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A. 1995;92(19):8734–8.PubMedCrossRef

36.

Jockers R, Maurice P, Boutin JA, Delagrange P. Melatonin receptors, heterodimerization, signal transduction and binding sites: what’s new? Br J Pharmacol. 2008;154(6):1182–95.PubMedCrossRef

37.

Muhlbauer E, Gross E, Labucay K, Wolgast S, Peschke E. Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose. Eur J Pharmacol. 2009;606(1–3):61–71.PubMedCrossRef

38.

Peschke E, Muhlbauer E, Musshoff U, Csernus VJ, Chankiewitz E, Peschke D. 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.PubMedCrossRef

39.

Peschke E, Bach AG, Muhlbauer E. Parallel signaling pathways of melatonin in the pancreatic beta-cell. J Pineal Res. 2006;40(2):184–91.PubMedCrossRef

40.

Masana MI, Dubocovich ML. Melatonin receptor signaling: finding the path through the dark. Sci Stke. 2001;2001(107):39.CrossRef

41.

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):318–27.PubMedCrossRef

42.

Stumpf I, Bazwinsky I, Peschke E. Modulation of the cGMP signaling pathway by melatonin in pancreatic beta-cells. J Pineal Res. 2009;46(2):140–7.PubMedCrossRef

43.

•• Lyssenko V, Nagorny CL, Erdos MR, Wierup N, Jonsson A, Spegel P, et al. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2009;41(1):82–8. This study provides a comprehansive description of in vitro and in vivo effects of originally discovered common variant SNP rs10830963 in the MTNR1B gene on islet function and risk of type 2 diabetes.PubMedCrossRef

44.

• Bouatia-Naji N, Bonnefond A, Cavalcanti-Proenca C, Sparso 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(1):89–94. This is the first meta-analysis of genome-wide association studies for glucose and insulin levels. Together with another accompanying study (45) it identifies common variants in the MTNR1B gene to be associated with elevated glucose levels.PubMedCrossRef

45.

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(1):77–81.PubMedCrossRef

46.

Gonciarz M, Gonciarz Z, Bielanski W, Mularczyk A, Konturek PC, Brzozowski T, et al. The pilot study of 3-month course of melatonin treatment of patients with nonalcoholic steatohepatitis: effect on plasma levels of liver enzymes, lipids and melatonin. J Physiol Pharmacol: Off J Polish Physiol Soc. 2010;61(6):705–10.

47.

Walford GA, Green T, Neale B, Isakova T, Rotter JI, Grant SF, et al. Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. Diabetologia. 2012;55(2):331–9.PubMedCrossRef

48.

Barker A, Sharp SJ, Timpson NJ, Bouatia-Naji N, Warrington NM, Kanoni S, et al. Association of genetic Loci with glucose levels in childhood and adolescence: a meta-analysis of over 6000 children. Diabetes. 2011;60(6):1805–12.PubMedCrossRef

49.

•• Bonnefond A, Clement N, Fawcett K, Yengo L, Vaillant E, Guillaume JL, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44(3):297–301. This is a first large scale exon re-sequencing study of the MTNR1B gene. It provides the first evidence on a number of rare variants in the MTNR1B gene with partial- or total-loss-of-function properties.PubMedCrossRef

50.

Kwak SH, Kim SH, Cho YM, Go MJ, Cho YS, Choi SH, et al. A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes. 2012;61(2):531–41.PubMedCrossRef

51.

Vlassi M, Gazouli M, Paltoglou G, Christopoulos P, Florentin L, Kassi 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):70–6.

52.

Liao S, Liu Y, Tan Y, Gan L, Mei J, Song W, et al. Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women. PLoS One. 2012;7(7):e40113.PubMedCrossRef

53.

Wang Y, Nie M, Li W, Ping F, Hu Y, Ma L, et al. Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population. PLoS One. 2011;6(11):e26953.PubMedCrossRef

54.

Dietrich K, Birkmeier S, Schleinitz D, Breitfeld J, Enigk B, Muller I, et al. Association and evolutionary studies of the melatonin receptor 1B gene (MTNR1B) in the self-contained population of Sorbs from Germany. Diab Med: J Br Diabet Assoc. 2011;28(11):1373–80.CrossRef

55.

Muhlbauer E, Albrecht E, Hofmann K, Bazwinsky-Wutschke I, Peschke E. Melatonin inhibits insulin secretion in rat insulinoma beta-cells (INS-1) heterologously expressing the human melatonin receptor isoform MT2. J Pineal Res. 2011;51(3):361–72.PubMedCrossRef

56.

Sparso 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. Diabetes. 2009;58(6):1450–6.CrossRef

57.

Vangipurapu J, Stancakova A, Pihlajamaki J, Kuulasmaa TM, Kuulasmaa T, Paananen 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):563–71.PubMedCrossRef

58.

Garfinkel D, Zorin M, Wainstein J, Matas Z, Laudon M, Zisapel N. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes: Targets Ther. 2011;4:307–13.

59.

Peschke E, Hofmann K, Ponicke K, Wedekind D, Muhlbauer E. Catecholamines are the key for explaining the biological relevance of insulin-melatonin antagonisms in type 1 and type 2 diabetes. J Pineal Res. 2012;52(4):389–96.PubMedCrossRef

60.

Illig T, Gieger C, Zhai G, Romisch-Margl W, Wang-Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42(2):137–41.PubMedCrossRef

Titel: Tired of Diabetes Genetics? Circadian Rhythms and Diabetes: The MTNR1B Story?
verfasst von: Cecilia Nagorny
Valeriya Lyssenko
Publikationsdatum: 01.12.2012
Verlag: Current Science Inc.
Erschienen in: Current Diabetes Reports / Ausgabe 6/2012
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-012-0327-y

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