Increased Risk of Diabetes due to Obesity: Does Chronodisruption Play a Role?

  • Susanne E. la Fleur
  • Andries Kalsbeek


The prevalence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic β-cell dysfunction and visceral adiposity. Although it has been known for quite some time that a disruption of biological rhythms (as happens with shift work) increases the risk of developing obesity, insulin resistance and T2DM, more recent genomic evidence has further spiked the interest for the involvement of circadian rhythms (and their disruption) in the development of diabetes. In this chapter, we will start with an overview of the way in which glucose metabolism and the basal rhythm in plasma glucose concentrations and insulin sensitivity are regulated, after which we will discuss how a disruption of daily rhythms or a disruption of clock elements, may contribute to the development of insulin resistance.


Autonomic Nervous System Clock Gene Plasma Glucose Concentration Hepatic Glucose Production Plasma Insulin Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Feldberg W, Pyke D, Stubbs WA (1985) Hyperglycaemia: imitating Claude Bernard’s piqure with drugs. J Auton Nerv Syst 14(3):213–228PubMedGoogle Scholar
  2. 2.
    Kreier F, Swaab DF (2010) Chapter 23: history of neuroendocrinology “the spring of primitive existence”. Handb Clin Neurol 95:335–360PubMedGoogle Scholar
  3. 3.
    Cannon W (1929) Organization for physiological homeostasis. Physiol Rev 9(3):399–431Google Scholar
  4. 4.
    Cuesta M, Clesse D, Pevet P, Challet E (2009) From daily behavior to hormonal and neurotransmitters rhythms: comparison between diurnal and nocturnal rat species. Horm Behav 55(2):338–347PubMedGoogle Scholar
  5. 5.
    Carroll KF, Nestel PJ (1973) Diurnal variation in glucose tolerance and in insulin secretion in man. Diabetes 22(5):333–348PubMedGoogle Scholar
  6. 6.
    Lee A, Ader M, Bray GA, Bergman RN (1992) Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects. Diabetes 41(6):750–759PubMedGoogle Scholar
  7. 7.
    Whichelow MJ, Sturge RA, Keen H, Jarrett RJ, Stimmler L, Grainger S (1974) Diurnal variation in response to intravenous glucose. Br Med J 1(5906):488–491PubMedGoogle Scholar
  8. 8.
    Rusak B, Zucker I (1979) Neural regulation of circadian rhythms. Physiol Rev 59(3):449–526PubMedGoogle Scholar
  9. 9.
    Bartness TJ, Bamshad M (1998) Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. Am J Physiol 275(5 Pt 2):R1399–R1411PubMedGoogle Scholar
  10. 10.
    Buijs RM, Wortel J, Van Heerikhuize JJ, Feenstra MG, Ter Horst GJ, Romijn HJ, Kalsbeek A (1999) Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. Eur J Neurosci 11(5):1535–1544PubMedGoogle Scholar
  11. 11.
    Buijs RM, Chun SJ, Niijima A, Romijn HJ, Nagai K (2001) Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J Comp Neurol 431(4):405–423PubMedGoogle Scholar
  12. 12.
    Buijs RM, la Fleur SE, Wortel J, van Heijningen C, Zuiddam L, Mettenleiter TC, Kalsbeek A, Nagai K, Niijima A (2003) The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol 464(1):36–48PubMedGoogle Scholar
  13. 13.
    Jansen AS, Hoffman JL, Loewy AD (1997) CNS sites involved in sympathetic and parasympathetic control of the pancreas: a viral tracing study. Brain Res 766(1–2):29–38PubMedGoogle Scholar
  14. 14.
    la Fleur SE, Kalsbeek A, Wortel J, Buijs RM (2000) Polysynaptic neural pathways between the hypothalamus, including the suprachiasmatic nucleus, and the liver. Brain Res 871(1):50–56PubMedGoogle Scholar
  15. 15.
    Ueyama T, Krout KE, Nguyen XV, Karpitskiy V, Kollert A, Mettenleiter TC, Loewy AD (1999) Suprachiasmatic nucleus: a central autonomic clock. Nat Neurosci 2(12):1051–1053PubMedGoogle Scholar
  16. 16.
    Yamamoto H, Nagai K, Nakagawa H (1987) Role of SCN in daily rhythms of plasma glucose, FFA, insulin and glucagon. Chronobiol Int 4(4):483–491PubMedGoogle Scholar
  17. 17.
    Yamamoto H, Nagai K, Nakagawa H (1984) Bilateral lesions of the SCN abolish lipolytic and hyperphagic responses to 2DG. Physiol Behav 32(6):1017–1020PubMedGoogle Scholar
  18. 18.
    Strubbe JH, Prins AJ, Bruggink J, Steffens AB (1987) Daily variation of food-induced changes in blood glucose and insulin in the rat and the control by the suprachiasmatic nucleus and the vagus nerve. J Auton Nerv Syst 20(2):113–119PubMedGoogle Scholar
  19. 19.
    Escobar C, Diaz-Munoz M, Encinas F, Aguilar-Roblero R (1998) Persistence of metabolic rhythmicity during fasting and its entrainment by restricted feeding schedules in rats. Am J Physiol 274(5 Pt 2):R1309–R1316PubMedGoogle Scholar
  20. 20.
    Kalsbeek A, Strubbe JH (1998) Circadian control of insulin secretion is independent of the temporal distribution of feeding. Physiol Behav 63(4):553–558PubMedGoogle Scholar
  21. 21.
    Challet E, Pevet P, Vivien-Roels B, Malan A (1997) Phase-advanced daily rhythms of melatonin, body temperature, and locomotor activity in food-restricted rats fed during daytime. J Biol Rhythms 12(1):65–79PubMedGoogle Scholar
  22. 22.
    Choi S, Wong LS, Yamat C, Dallman MF (1998) Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator? J Neurosci 18(10):3843–3852PubMedGoogle Scholar
  23. 23.
    Kalsbeek A, Van Heerikhuize JJ, Wortel J, Buijs RM (1998) Restricted daytime feeding modifies suprachiasmatic nucleus vasopressin release in rats. J Biol Rhythms 13(1):18–29PubMedGoogle Scholar
  24. 24.
    la Fleur SE, Kalsbeek A, Wortel J, Buijs RM (1999) A suprachiasmatic nucleus generated rhythm in basal glucose concentrations. J Neuroendocrinol 11(8):643–652PubMedGoogle Scholar
  25. 25.
    Boden G, Ruiz J, Urbain JL, Chen X (1996) Evidence for a circadian rhythm of insulin secretion. Am J Physiol 271(2 Pt 1):E246–E252PubMedGoogle Scholar
  26. 26.
    Dallman MF, Akana SF, Bhatnagar S, Bell ME, Choi S, Chu A, Horsley C, Levin N, Meijer O, Soriano LR et al (1999) Starvation: early signals, sensors, and sequelae. Endocrinology 140(9):4015–4023PubMedGoogle Scholar
  27. 27.
    la Fleur SE, Kalsbeek A, Wortel J, Fekkes ML, Buijs RM (2001) A daily rhythm in glucose tolerance: a role for the suprachiasmatic nucleus. Diabetes 50(6):1237–1243PubMedGoogle Scholar
  28. 28.
    Bolli GB, Gerich JE (1984) The “dawn phenomenon”—a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus. N Engl J Med 310(12):746–750PubMedGoogle Scholar
  29. 29.
    Kalsbeek A, la Fleur SE, van Heijningen C, Buijs RM (2004) Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver. J Neurosci 24(35):7604–7613PubMedGoogle Scholar
  30. 30.
    Fujii T, Inoue S, Nagai K, Nakagawa H (1989) Involvement of adrenergic mechanism in hyperglycemia due to SCN stimulation. Horm Metab Res 21(12):643–645PubMedGoogle Scholar
  31. 31.
    Nagai K, Fujii T, Inoue S, Takamura Y, Nakagawa H (1988) Electrical stimulation of the suprachiasmatic nucleus of the hypothalamus causes hyperglycemia. Horm Metab Res 20(1):37–39PubMedGoogle Scholar
  32. 32.
    Cailotto C, van Heijningen C, van der Vliet J, van der Plasse G, Habold C, Kalsbeek A, Pevet P, Buijs RM (2008) Daily rhythms in metabolic liver enzymes and plasma glucose require a balance in the autonomic output to the liver. Endocrinology 149(4):1914–1925PubMedGoogle Scholar
  33. 33.
    la Fleur SE (2001) The suprachiasmatic nucleus generated rhythm in blood glucose. Thesis, University of Amsterdam, the NetherlandsGoogle Scholar
  34. 34.
    Buijs RM (1978) Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat. Pathways to the limbic system, medulla oblongata and spinal cord. Cell Tissue Res 192(3):423–435PubMedGoogle Scholar
  35. 35.
    Jansen AS, Farwell DG, Loewy AD (1993) Specificity of pseudorabies virus as a retrograde marker of sympathetic preganglionic neurons: implications for transneuronal labeling studies. Brain Res 617(1):103–112PubMedGoogle Scholar
  36. 36.
    Luiten PG, Ter Horst GJ, Karst H, Steffens AB (1985) The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res 329(1–2):374–378PubMedGoogle Scholar
  37. 37.
    Swanson LW, McKellar S (1979) The distribution of oxytocin- and neurophysin-stained fibers in the spinal cord of the rat and monkey. J Comp Neurol 188(1):87–106PubMedGoogle Scholar
  38. 38.
    Kalsbeek A, Ruiter M, la Fleur SE, Cailotto C, Kreier F, Buijs RM (2006) The hypothalamic clock and its control of glucose homeostasis. Prog Brain Res 153:283–307PubMedGoogle Scholar
  39. 39.
    Kalsbeek A, Foppen E, Schalij I, van Heijningen C, van de Vliet J, Fliers E, Buijs RM (2008) Circadian control of the daily plasma glucose rhythm: an interplay of GABA and glutamate. PLoS One 3(9):e3194PubMedGoogle Scholar
  40. 40.
    Yi CX, Serlie MJ, Ackermans MT, Foppen E, Buijs RM, Sauerwein HP, Fliers E, Kalsbeek A (2009) A major role for perifornical orexin neurons in the control of glucose metabolism in rats. Diabetes 58(9):1998–2005PubMedGoogle Scholar
  41. 41.
    Vrang N, Mikkelsen JD, Larsen PJ (1997) Direct link from the suprachiasmatic nucleus to hypothalamic neurons projecting to the spinal cord: a combined tracing study using cholera toxin subunit B and Phaseolus vulgaris-leucoagglutinin. Brain Res Bull 44(6):671–680PubMedGoogle Scholar
  42. 42.
    van den Top M, Lee K, Whyment AD, Blanks AM, Spanswick D (2004) Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nat Neurosci 7(5):493–494PubMedGoogle Scholar
  43. 43.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432PubMedGoogle Scholar
  44. 44.
    Burdakov D, Gonzalez JA (2009) Physiological functions of glucose-inhibited neurones. Acta Physiol (Oxf) 195(1):71–78Google Scholar
  45. 45.
    Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA (2004) Neuronal glucosensing: what do we know after 50 years? Diabetes 53(10):2521–2528PubMedGoogle Scholar
  46. 46.
    de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS et al (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95(1):322–327Google Scholar
  47. 47.
    Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98(3):365–376PubMedGoogle Scholar
  48. 48.
    Shiuchi T, Haque MS, Okamoto S, Inoue T, Kageyama H, Lee S, Toda C, Suzuki A, Bachman ES, Kim YB et al (2009) Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab 10(6):466–480PubMedGoogle Scholar
  49. 49.
    Zhang S, Zeitzer JM, Yoshida Y, Wisor JP, Nishino S, Edgar DM, Mignot E (2004) Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep 27(4):619–627PubMedGoogle Scholar
  50. 50.
    Scheen AJ, Buxton OM, Jison M, van Reeth O, Leproult R, L’Hermite-Baleriaux M, Van Cauter E (1998) Effects of exercise on neuroendocrine secretions and glucose regulation at different times of day. Am J Physiol 274(6 Pt 1):E1040–E1049PubMedGoogle Scholar
  51. 51.
    Kalsbeek A, Ruiter M, la Fleur SE, van Heijningen C, Bujis RM (2003) The diurnal modulation of hormonal responses in the rat varies with different stimuli. J Neuroendocrinol 15(12):1144–1155PubMedGoogle Scholar
  52. 52.
    Jasper MS, Engeland WC (1994) Splanchnic neural activity modulates ultradian and circadian rhythms in adrenocortical secretion in awake rats. Neuroendocrinology 59(2):97–109PubMedGoogle Scholar
  53. 53.
    Kaneko M, Kaneko K, Shinsako J, Dallman MF (1981) Adrenal sensitivity to adrenocorticotropin varies diurnally. Endocrinology 109(1):70–75PubMedGoogle Scholar
  54. 54.
    Kalsbeek A, van der Spek R, Lei J, Endert E, Buijs RM, Fliers E (2012) Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol 349(1):20–29PubMedGoogle Scholar
  55. 55.
    Ruiter M, la Fleur SE, van Heijningen C, van der Vleit J, Kalsbeek A, Buijs RM (2003) The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Diabetes 52(7):1709–1715PubMedGoogle Scholar
  56. 56.
    Dallman MF, Strack AM, Akana SF, Bradbury MJ, Hanson ES, Scribner KA, Smith M (1993) Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol 14(4):303–347PubMedGoogle Scholar
  57. 57.
    De Boer SF, Van der Gugten J (1987) Daily variations in plasma noradrenaline, adrenaline and corticosterone concentrations in rats. Physiol Behav 40(3):323–328PubMedGoogle Scholar
  58. 58.
    Kalsbeek A, van der Vliet J, Buijs RM (1996) Decrease of endogenous vasopressin release necessary for expression of the circadian rise in plasma corticosterone: a reverse microdialysis study. J Neuroendocrinol 8(4):299–307PubMedGoogle Scholar
  59. 59.
    Trumper BG, Reschke K, Molling J (1995) Circadian variation of insulin requirement in insulin dependent diabetes mellitus the relationship between circadian change in insulin demand and diurnal patterns of growth hormone, cortisol and glucagon during euglycemia. Horm Metab Res 27(3):141–147PubMedGoogle Scholar
  60. 60.
    van Cauter E (1990) Diurnal and ultradian rhythms in human endocrine function: a minireview. Horm Res 34(2):45–53Google Scholar
  61. 61.
    Bright GM, Melton TW, Rogol AD, Clarke WL (1980) Failure of cortisol blockade to inhibit early morning increases in basal insulin requirements in fasting insulin-dependent diabetics. Diabetes 29(8):662–664PubMedGoogle Scholar
  62. 62.
    Cailotto C, la Fleur SE, van Heijningen C, Wortel J, Kalsbeek A, Feenstra M, Pevet P, Bujis RM (2005) The suprachiasmatic nucleus controls the daily variation of plasma glucose via the autonomic output to the liver: are the clock genes involved? Eur J Neurosci 22(10):2531–2540PubMedGoogle Scholar
  63. 63.
    Clark RG, Chambers G, Lewin J, Robinson IC (1986) Automated repetitive microsampling of blood: growth hormone profiles in conscious male rats. J Endocrinol 111(1):27–35PubMedGoogle Scholar
  64. 64.
    Kimura F, Tsai CW (1984) Ultradian rhythm of growth hormone secretion and sleep in the adult male rat. J Physiol 353:305–315PubMedGoogle Scholar
  65. 65.
    DeFronzo RA (2010) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53(7):1270–1287PubMedGoogle Scholar
  66. 66.
    DeFronzo RA, Simonson D, Ferrannini E (1982) Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia 23(4):313–319PubMedGoogle Scholar
  67. 67.
    Butler AE, Janson J, Soeller WC, Butler PC (2003) Increased beta-cell apoptosis prevents adaptive increase in beta-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes 52(9):2304–2314PubMedGoogle Scholar
  68. 68.
    Perley MJ, Kipnis DM (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46(12):1954–1962PubMedGoogle Scholar
  69. 69.
    Yki-Jarvinen H (1995) Role of insulin resistance in the pathogenesis of NIDDM. Diabetologia 38(12):1378–1388PubMedGoogle Scholar
  70. 70.
    Florez JC (2008) Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia 51(7):1100–1110PubMedGoogle Scholar
  71. 71.
    Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42(7):579–589PubMedGoogle Scholar
  72. 72.
    Karlsson B, Knutsson A, Lindahl B (2001) Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med 58(11):747–752PubMedGoogle Scholar
  73. 73.
    Kroenke CH, Spiegelman D, Manson J, Schernhammer ES, Colditz GA, Kawachi I (2007) Work characteristics and incidence of type 2 diabetes in women. Am J Epidemiol 165(2):175–183PubMedGoogle Scholar
  74. 74.
    Morikawa Y, Nakagawa H, Miura K, Soyama Y, Ishizaki M, Kido T, Naruse Y, Suwazono Y, Nogawa K (2007) Effect of shift work on body mass index and metabolic parameters. Scand J Work Environ Health 33(1):45–50PubMedGoogle Scholar
  75. 75.
    Scheer FA, Hilton MF, Mantzoros CS, Shea SA (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 106(11):4453–4458PubMedGoogle Scholar
  76. 76.
    Roenneberg T, Wirz-Justice A, Merrow M (2003) Life between clocks: daily temporal patterns of human chronotypes. J Biol Rhythms 18(1):80–90PubMedGoogle Scholar
  77. 77.
    Roenneberg T, Kuehnle T, Pramstaller PP, Ricken J, Havel M, Guth A, Merrow M (2004) A marker for the end of adolescence. Curr Biol 14(24):R1038–R1039PubMedGoogle Scholar
  78. 78.
    van Cauter E (2011) Sleep disturbances and insulin resistance. Diabet Med 28(12):1455–1462Google Scholar
  79. 79.
    Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417(6884):78–83PubMedGoogle Scholar
  80. 80.
    Muhlbauer E, Wolgast S, Finckh U, Peschke D, Peschke E (2004) Indication of circadian oscillations in the rat pancreas. FEBS Lett 564(1–2):91–96PubMedGoogle Scholar
  81. 81.
    Zvonic S, Ptitsyn AA, Conrad SA, Scott LK, Floyd ZE, Kilroy G, Wu X, Goh BC, Mynatt RL, Gimble JM (2006) Characterization of peripheral circadian clocks in adipose tissues. Diabetes 55(4):962–970PubMedGoogle Scholar
  82. 82.
    Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418(6901):935–941PubMedGoogle Scholar
  83. 83.
    Damiola F, Le MN, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14(23):2950–2961PubMedGoogle Scholar
  84. 84.
    Dufour CR, Levasseur MP, Pham NH, Eichner LJ, Wilson BJ, Charest-Marcotte A, Duguay D, Poirier-Heon JF, Cermakian N, Giguere V (2011) Genomic convergence among ERRalpha, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS Genet 7(6):e1002143PubMedGoogle Scholar
  85. 85.
    Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ et al (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326(5951):437–440PubMedGoogle Scholar
  86. 86.
    Liu C, Li S, Liu T, Borjigin J, Lin JD (2007) Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 447(7143):477–481PubMedGoogle Scholar
  87. 87.
    Hsieh MC, Yang SC, Tseng HL, Hwang LL, Chen CT, Shieh KR (2010) Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long-term, high-fat-diet-treated mice. Int J Obes (Lond) 34(2):227–239Google Scholar
  88. 88.
    Barnea M, Madar Z, Froy O (2010) High-fat diet followed by fasting disrupts circadian expression of adiponectin signaling pathway in muscle and adipose tissue. Obesity (Silver Spring) 18(2):230–238Google Scholar
  89. 89.
    Barnea M, Madar Z, Froy O (2009) High-fat diet delays and fasting advances the circadian expression of adiponectin signaling components in mouse liver. Endocrinology 150(1):161–168PubMedGoogle Scholar
  90. 90.
    Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y, Turek FW, Bass J (2007) High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6(5):414–421PubMedGoogle Scholar
  91. 91.
    Sutton GM, Centanni AV, Butler AA (2010) Protein malnutrition during pregnancy in C57BL/6J mice results in offspring with altered circadian physiology before obesity. Endocrinology 151(4):1570–1580PubMedGoogle Scholar
  92. 92.
    Ando H, Ushijima K, Yanagihara H, Hayashi Y, Takamura T, Kaneko S, Fujimura A (2009) Clock gene expression in the liver and adipose tissues of non-obese type 2 diabetic Goto-Kakizaki rats. Clin Exp Hypertens 31(3):201–207PubMedGoogle Scholar
  93. 93.
    Otway DT, Mantele S, Bretschneider S, Wright J, Trayhurn P, Skene DJ, Robertson MD, Johnston JD (2011) Rhythmic diurnal gene expression in human adipose tissue from individuals who are lean, overweight, and type 2 diabetic. Diabetes 60(5):1577–1581PubMedGoogle Scholar
  94. 94.
    Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308(5724):1043–1045PubMedGoogle Scholar
  95. 95.
    Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH et al (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466(7306):627–631PubMedGoogle Scholar
  96. 96.
    Oishi K, Ohkura N, Wakabayashi M, Shirai H, Sato K, Matsuda J, Atsumi G, Ishida N (2006) CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression. J Thromb Haemost 4(8):1774–1780PubMedGoogle Scholar
  97. 97.
    Sadacca LA, Lamia KA, DeLemos AS, Blum B, Weitz CJ (2011) An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice. Diabetologia 54(1):120–124PubMedGoogle Scholar
  98. 98.
    Vieira E, Marroqui L, Batista TM, Caballero-Garrido E, Carneiro EM, Boschero AC, Nadal A, Quesada I (2012) The clock gene Rev-erbalpha regulates pancreatic beta-cell function: modulation by leptin and high-fat diet. Endocrinology 153(2):592–601PubMedGoogle Scholar
  99. 99.
    Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42(2):105–116PubMedGoogle Scholar
  100. 100.
    Liu C, Li H, Qi L, Loos RJ, Qi Q, Lu L, Gan W, Lin X (2011) Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans. PLoS One 6(6):e21464PubMedGoogle Scholar
  101. 101.
    Oishi K, Atsumi G, Sugiyama S, Kodomari I, Kasamatsu M, Machida K, Ishida N (2006) Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice. FEBS Lett 580(1):127–130PubMedGoogle Scholar
  102. 102.
    Kennaway DJ, Owens JA, Voultsios A, Boden MJ, Varcoe TJ (2007) Metabolic homeostasis in mice with disrupted Clock gene expression in peripheral tissues. Am J Physiol Regul Integr Comp Physiol 293(4):R1528–R1537PubMedGoogle Scholar
  103. 103.
    Toye AA, Lippiat JD, Proks P, Shimomura K, Bentley L, Hugill A, Mijat V, Goldsworthy M, Moir L, Haynes A et al (2005) A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 48(4):675–686PubMedGoogle Scholar
  104. 104.
    Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103(7):1009–1017PubMedGoogle Scholar
  105. 105.
    Dallmann R, Touma C, Palme R, Albrecht U, Steinlechner S (2006) Impaired daily glucocorticoid rhythm in Per1 ( Brd ) mice. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 192(7):769–775PubMedGoogle Scholar
  106. 106.
    Raspe E, Mautino G, Duval C, Fontaine C, Duez H, Barbier O, Monte D, Fruchart J, Fruchart JC, Staels B (2002) Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha. J Biol Chem 277(51):49275–49281PubMedGoogle Scholar
  107. 107.
    Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U (2007) System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5(2):e34PubMedGoogle Scholar
  108. 108.
    Bray MS, Young ME (2009) The role of cell-specific circadian clocks in metabolism and disease. Obes Rev 10(Suppl 2):6–13PubMedGoogle Scholar
  109. 109.
    Lamia KA, Storch KF, Weitz CJ (2008) Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci USA 105(39):15172–15177PubMedGoogle Scholar
  110. 110.
    Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB et al (2007) Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science 318(5857):1786–1789PubMedGoogle Scholar
  111. 111.
    Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC, Hirota T, Nusinow DA, Sun X, Landais S, Kodama Y et al (2010) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med 16(10):1152–1156PubMedGoogle Scholar
  112. 112.
    Kalsbeek A, Yi CX, la Fleur SE, Fliers E (2010) The hypothalamic clock and its control of glucose homeostasis. Trends Endocrinol Metab 21(7):402410PubMedGoogle Scholar
  113. 113.
    Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134(5):728–742.PubMedGoogle Scholar
  114. 114.
    Nagai K and Nakagawa H (1992) Central Regulation of Energy Metabolism with special reference to circadian rhythm. CRC Press, Boca Raton, FloridaPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Hypothalamic Integration MechanismsNetherlands Institute for NeuroscienceAmsterdamThe Netherlands

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