Current Diabetes Reports

, 14:474 | Cite as

Does Disruption of Circadian Rhythms Contribute to Beta-Cell Failure in Type 2 Diabetes?

  • Kuntol Rakshit
  • Anthony P. Thomas
  • Aleksey V. Matveyenko
Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by the loss of beta-cell secretory function and mass. The pathophysiology of beta-cell failure in T2DM involves a complex interaction between genetic susceptibilities and environmental risk factors. One environmental condition that is gaining greater appreciation as a risk factor for T2DM is the disruption of circadian rhythms (eg, shift-work and sleep loss). In recent years, circadian disruption has become increasingly prevalent in modern societies and consistently shown to augment T2DM susceptibility (partly mediated through its effects on pancreatic beta-cells). Since beta-cell failure is essential for development of T2DM, we will review current work from epidemiologic, clinical, and animal studies designed to gain insights into the molecular and physiological mechanisms underlying the predisposition to beta-cell failure associated with circadian disruption. Elucidating the role of circadian clocks in regulating beta-cell health will add to our understanding of T2DM pathophysiology and may contribute to the development of novel therapeutic and preventative approaches.

Keywords

Circadian rhythms Circadian clocks Circadian disruption Hyperglycemia Type 2 diabetes Insulin secretion Beta-cell mass Oxidative stress Beta-cell failure 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    DeFronzo RA, Abdul-Ghani MA. Preservation of beta-cell function: the key to diabetes prevention. J Clin Endocrinol Metab. 2011;96:2354–66.PubMedCrossRefGoogle Scholar
  2. 2.
    Brunzell JD, Robertson RP, Lerner RL, et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab. 1976;42:222–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Seltzer HS, Allen EW, Herron Jr AL, et al. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967;46:323–35.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Hojberg PV, Vilsboll T, Rabol R, et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 2009;52:199–207.PubMedCrossRefGoogle Scholar
  5. 5.
    Ward WK, Bolgiano DC, McKnight B, et al. Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest. 1984;74:1318–28.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Porksen N, Hollingdal M, Juhl C, et al. Pulsatile insulin secretion: detection, regulation, and role in diabetes. Diabetes. 2002;51 Suppl 1:S245–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Pimenta W, Korytkowski M, Mitrakou A, et al. Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. JAMA. 1995;273:1855–61.PubMedCrossRefGoogle Scholar
  8. 8.
    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;51:1100–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Meier JJ, Bonadonna RC. Role of reduced beta-cell mass versus impaired beta-cell function in the pathogenesis of type 2 diabetes. Diabetes Care. 2013;36 Suppl 2:S113–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Butler AE, Janson J, Bonner-Weir S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52:102–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Rahier J, Guiot Y, Goebbels RM, et al. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008;10 Suppl 4:32–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Sakuraba H, Mizukami H, Yagihashi N, et al. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia. 2002;45:85–96.PubMedCrossRefGoogle Scholar
  13. 13.
    Yoon KH, Ko SH, Cho JH, et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab. 2003;88:2300–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoneda S, Uno S, Iwahashi H, et al. Predominance of beta-cell neogenesis rather than replication in humans with an impaired glucose tolerance and newly diagnosed diabetes. J Clin Endocrinol Metab. 2013;98:2053–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Marchetti P, Del Guerra S, Marselli L, et al. Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab. 2004;89:5535–41.PubMedCrossRefGoogle Scholar
  16. 16.
    Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002;110:851–60.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Robertson RP. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem. 2004;279:42351–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Poitout V, Robertson RP. Minireview: secondary beta-cell failure in type 2 diabetes–a convergence of glucotoxicity and lipotoxicity. Endocrinology. 2002;143:339–42.PubMedGoogle Scholar
  19. 19.
    Haataja L, Gurlo T, Huang CJ, et al. Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev. 2008;29:303–16.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Shu L, Sauter NS, Schulthess FT, et al. Transcription factor 7-like 2 regulates beta-cell survival and function in human pancreatic islets. Diabetes. 2008;57:645–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Newsholme P, Haber EP, Hirabara SM, et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and nonmitochondrial ROS production and activity. J Physiol. 2007;583:9–24.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Schuit F, De Vos A, Farfari S, et al. Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem. 1997;272:18572–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Matschinsky FM, Glaser B, Magnuson MA. Pancreatic beta-cell glucokinase: closing the gap between theoretical concepts and experimental realities. Diabetes. 1998;47:307–15.PubMedCrossRefGoogle Scholar
  24. 24.
    Matschinsky FM. Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. Diabetes. 1990;39:647–52.PubMedCrossRefGoogle Scholar
  25. 25.
    Ishihara H, Wang H, Drewes LR, et al. Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. J Clin Invest. 1999;104:1621–9.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev. 2005;85:1303–42.PubMedCrossRefGoogle Scholar
  27. 27.
    Andersson SA, Olsson AH, Esguerra JL, et al. Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes. Mol Cell Endocrinol. 2012;364:36–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Del Guerra S, Lupi R, Marselli L, et al. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes. 2005;54:727–35.PubMedCrossRefGoogle Scholar
  29. 29.
    MacDonald MJ, Longacre MJ, Langberg EC, et al. Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes. Diabetologia. 2009;52:1087–91.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Maechler P, Wollheim CB. Mitochondrial function in normal and diabetic beta-cells. Nature. 2001;414:807–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Rosengren AH, Braun M, Mahdi T, et al. Reduced insulin exocytosis in human pancreatic beta-cells with gene variants linked to type 2 diabetes. Diabetes. 2012;61:1726–33.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Guo S, Dai C, Guo M, et al. Inactivation of specific β cell transcription factors in type 2 diabetes. J Clin Invest. 2013. doi:10.1172/JCI65390.
  33. 33.
    Silva CM, Sato S, Margolis RN. No time to lose: workshop on circadian rhythms and metabolic disease. Genes Dev. 2010;24:1456–64.Google Scholar
  34. 34.
    Bass J, Takahashi JS. Circadian integration of metabolism and energetics. Science. 2010;330:1349–54.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Reddy AB, O'Neill JS. Healthy clocks, healthy body, healthy mind. Trends Cell Biol. 2010;20:36–44.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418:935–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295:1070–3.PubMedCrossRefGoogle Scholar
  38. 38.
    Hattar S, Liao HW, Takao M, et al. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002;295:1065–70.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Buijs RM, Kalsbeek A. Hypothalamic integration of central and peripheral clocks. Nat Rev Neurosci. 2001;2:521–6.PubMedCrossRefGoogle Scholar
  40. 40.•
    Marcheva B, Ramsey KM, Buhr ED, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010;466:627–31. First demonstration that targeted disruption of beta-cell molecular clock results in beta-cell failure and T2DM. The study was also the first to show that (1) pancreatic islets express self-sustained oscillations of clock genes, (2) disruption of the beta-cell circadian clock leads to hyperglycemia and overt glucose-intolerance, and (3) genetic disruption of the beta-cell circadian clock leads to impaired GSIS both in vitro and in vivo.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Saini C, Suter DM, Liani A, et al. The mammalian circadian timing system: synchronization of peripheral clocks. Cold Spring Harb Symp Quant Biol. 2011;76:39–47.Google Scholar
  42. 42.
    Takahashi JS, Hong HK, Ko CH, et al. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 2008;9:764–75.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Gekakis N, Staknis D, Nguyen HB, et al. Role of the CLOCK protein in the mammalian circadian mechanism. Science. 1998;280:1564–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Dunlap JC. Molecular bases for circadian clocks. Cell. 1999;96:271–90.PubMedCrossRefGoogle Scholar
  45. 45.
    Preitner N, Damiola F, Lopez-Molina L, et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002;110:251–60.PubMedCrossRefGoogle Scholar
  46. 46.
    Guillaumond F, Dardente H, Giguere V, et al. Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythm. 2005;20:391–403.CrossRefGoogle Scholar
  47. 47.
    Green CB, Takahashi JS, Bass J. The meter of metabolism. Cell. 2008;134:728–42.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Wyse CA, Selman C, Page MM, et al. Circadian desynchrony and metabolic dysfunction: did light pollution make us fat? Med Hypotheses. 2011;77:1139–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Beihl DA, Liese AD, Haffner SM. Sleep duration as a risk factor for incident type 2 diabetes in a multiethnic cohort. Ann Epidemiol. 2009;19:351–7.PubMedCrossRefGoogle Scholar
  50. 50.
    US Congress OTA. Biological rythms: implications for the worker, OTA-BA-463. Washington DC: US Government Printing Office; 1991.Google Scholar
  51. 51.
    Basner M, Fomberstein KM, Razavi FM, et al. American time use survey: sleep time and its relationship to waking activities. Sleep. 2007;30:1085–95.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Rutter J, Reick M, McKnight SL. Metabolism and the control of circadian rhythms. Annu Rev Biochem. 2002;71:307–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Kroenke CH, Spiegelman D, Manson J, et al. Work characteristics and incidence of type 2 diabetes in women. Am J Epidemiol. 2007;165:175–83.PubMedCrossRefGoogle Scholar
  54. 54.
    Mikuni E, Ohoshi T, Hayashi K, et al. Glucose intolerance in an employed population. Tohoku J Exp Med. 1983;141(Suppl):251–6.PubMedCrossRefGoogle Scholar
  55. 55.•
    Pan A, Schernhammer ES, Sun Q, et al. Rotating night shift work and risk of type 2 diabetes: 2 prospective cohort studies in women. PLoS Med. 2011;8:e1001141. The largest and most extensive prospective cohort study to date with ~20-year follow-up, found an increased risk of T2DM following chronic exposure to rotating shift work in women.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Suwazono Y, Dochi M, Oishi M, et al. Shiftwork and impaired glucose metabolism: a 14-year cohort study on 7104 male workers. Chronobiol Int. 2009;26:926–41.PubMedCrossRefGoogle Scholar
  57. 57.
    Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population. Diabetes Care. 2005;28:2762–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Meisinger C, Heier M, Loewel H. Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population. Diabetologia. 2005;48:235–41.PubMedCrossRefGoogle Scholar
  59. 59.
    Nilsson PM, Roost M, Engstrom G, et al. Incidence of diabetes in middle-aged men is related to sleep disturbances. Diabetes Care. 2004;27:2464–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care. 2006;29:657–61.PubMedCrossRefGoogle Scholar
  61. 61.•
    Buxton OM, Cain SW, O'Connor SP, et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012;4:129ra143. The first clear demonstration that exposure to circadian misalignment (with concurrent sleep restriction) for 3 weeks in otherwise healthy humans results in loss of appropriate beta-cell function.CrossRefGoogle Scholar
  62. 62.
    Buxton OM, Pavlova M, Reid EW, et al. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes. 2010;59:2126–33.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Qin LQ, Li J, Wang Y, et al. The effects of nocturnal life on endocrine circadian patterns in healthy adults. Life Sci. 2003;73:2467–75.PubMedCrossRefGoogle Scholar
  64. 64.•
    Scheer FA, Hilton MF, Mantzoros CS, et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106:4453–8. Study reports that 10 days circadian misalignment caused the subjects to exhibit postprandial hyperglycemia and glucose intolerance, with a subset of individuals (~40 %) notably exhibiting glucose intolerance values classified as “prediabetic” according to the current diagnostic criteria.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354:1435–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Gonnissen HK, Rutters F, Mazuy C, et al. Effect of a phase advance and phase delay of the 24-hour cycle on energy metabolism, appetite, and related hormones. Am J Clin Nutr. 2012;96:689–97.PubMedCrossRefGoogle Scholar
  67. 67.
    Boden G, Ruiz J, Urbain JL, et al. Evidence for a circadian rhythm of insulin secretion. Am J Physiol. 1996;271:E246–52.PubMedGoogle Scholar
  68. 68.
    Freinkel N, Mager M, Vinnick L. Cyclicity in the interrelationships between plasma insulin and glucose during starvation in normal young men. J Lab Clin Med. 1968;71:171–8.PubMedGoogle Scholar
  69. 69.
    Saad A, Dalla Man C, Nandy DK, et al. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012;61:2691–700.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Spiegel K, Knutson K, Leproult R, et al. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol. 2005;99:2008–19.PubMedCrossRefGoogle Scholar
  71. 71.
    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;42:105–16.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    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;41:82–8.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Prokopenko I, Langenberg C, Florez JC, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009;41:77–81.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    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;41:89–94.PubMedCrossRefGoogle Scholar
  75. 75.
    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 Rhythm. 2011;26:423–33.CrossRefGoogle Scholar
  76. 76.
    Lamia KA, Storch KF, Weitz CJ. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A. 2008;105:15172–7.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Lee J, Kim MS, Li R, et al. Loss of Bmal1 leads to uncoupling and impaired glucose-stimulated insulin secretion in beta-cells. Islets. 2011;3:381–8.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.•
    Qian J, Block GD, Colwell CS, et al. Consequences of exposure to light at night on the pancreatic islet circadian clock and function in rats. Diabetes. 2013;62:3469–78. This study first demonstrated that circadian misalignment induced by 10 weeks exposure to constant light significantly alters the islet circadian clock function through impairment in the amplitude, phase, and inter-islet synchrony of clock gene oscillations.PubMedCrossRefGoogle Scholar
  79. 79.
    Sadacca LA, Lamia KA, de Lemos AS, et al. An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice. Diabetologia. 2011;54:120–4.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Turek FW, Joshu C, Kohsaka A, et al. Obesity and metabolic syndrome in circadian clock mutant mice. Science. 2005;308:1043–5.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Vieira E, Marroqui L, Batista TM, et al. The clock gene Rev-erbalpha regulates pancreatic beta-cell function: modulation by leptin and high-fat diet. Endocrinology. 2012;153:592–601.PubMedCrossRefGoogle Scholar
  82. 82.•
    Lee J, Moulik M, Fang Z, et al. Bmal1 and beta-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced beta-cell failure in mice. Mol Cell Biol. 2013;33:2327–38. This work was the first to report that beta-cell failure consequent to beta-cell clock disruption is attributed to reduced antioxidant gene expression, mitochondrial dysfunction, and oxidative stress-induced mitochondrial uncoupling.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Pi J, Collins S. Reactive oxygen species and uncoupling protein 2 in pancreatic beta-cell function. Diabetes Obes Metab. 2010;12 Suppl 2:141–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Wilking M, Ndiaye M, Mukhtar H, et al. Circadian rhythm connections to oxidative stress: implications for human health. Antioxid Redox Signal. 2013;19:192–208.PubMedCrossRefGoogle Scholar
  85. 85.
    Kondratov RV, Kondratova AA, Gorbacheva VY, et al. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev. 2006;20:1868–73.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kuntol Rakshit
    • 1
  • Anthony P. Thomas
    • 1
  • Aleksey V. Matveyenko
    • 1
  1. 1.Larry L. Hillblom Islet Research Center, Department of Medicine, Division of EndocrinologyUniversity of California Los Angeles, David Geffen School of Medicine, Los Angeles, CaliforniaLos AngelesUSA

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