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Diabetes and Tryptophan Metabolism

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Tryptophan Metabolism: Implications for Biological Processes, Health and Disease

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Tryptophan, an essential amino acid, can be metabolized to several kinds of physiologically active metabolites. Accumulating data indicate that an altered metabolism of tryptophan and its active metabolites have important roles for the pathogenesis and development of complications of diabetes mellitus. Changes in tryptophan–kynurenine and tryptophan–methoxyindole pathways are related to several pathophysiological mechanisms of type 1 or type 2 diabetes. Particularly, serotonin, melatonin, and their receptors would be novel targets not only to better understand the pathogenesis of diabetes but also to develop new antidiabetic agents.

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References

  • (1997) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20:1183–1197

    Google Scholar 

  • (2011) Diagnosis and classification of diabetes mellitus. Diabetes Care 34(Suppl 1):S62–S69

    Google Scholar 

  • Allegrı G, Zaccarın D, Ragazzı E, Froldı G, Bertazzo A, Costa CV (2003) Metabolism of tryptophan along the kynurenine pathway in alloxan diabetic rabbits. Adv Exp Med Biol 527:387–393

    PubMed  Google Scholar 

  • Almawı WY, Tamım H, Azar ST (1999) Clinical review 103: T helper type 1 and 2 cytokines mediate the onset and progression of type I (insulin-dependent) diabetes. J Clin Endocrinol Metab 84:1497–1502

    PubMed  Google Scholar 

  • Aquılına JA, Carver JA, Truscott RJ (1997) Oxidation products of 3-hydroxykynurenine bind to lens proteins: relevance for nuclear cataract. Exp Eye Res 64:727–735

    PubMed  Google Scholar 

  • Atkınson MA, Maclaren NK (1994) The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med 331:1428–1436

    PubMed  Google Scholar 

  • Aurıcchıo S, Quaglıarıello E, Rubıno A, Vecchıone L (1960) Studies on the spontaneous urinary elimination of metabolites from the tryptophan-nicotinic acid pathway in children afflicted by various diseases. Ann Paediatr 194:129–140

    PubMed  Google Scholar 

  • Baban B, Hansen AM, Chandler PR, Manlapat A, Bıngaman A, Kahler DJ, Munn DH, Mellor AL (2005) A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int Immunol 17:909–919

    CAS  PubMed  Google Scholar 

  • Baekkeskov S, Aanstoot HJ, Chrıstgau S, Reetz A, Solımena M, Cascalho M, Follı F, Rıchter-Olesen H, DE Camıllı P (1990) Identification of the 64 K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347:151–156

    CAS  PubMed  Google Scholar 

  • Bazwınsky-Wutschke I, Bıeseke L, Muhlbauer E, Peschke E (2014) Influence of melatonin receptor signalling on parameters involved in blood glucose regulation. J Pineal Res 56:82–96

    PubMed  Google Scholar 

  • Belladonna ML, Puccettı P, Orabona C, Fallarıno F, Vacca C, Volpı C, Gızzı S, Pallotta MT, Fıorettı MC, Grohmann U (2007) Immunosuppression via tryptophan catabolism: the role of kynurenine pathway enzymes. Transplantation 84:S17–S20

    CAS  PubMed  Google Scholar 

  • Bender DA, Njagı EN, Danıelıan PS (1990) Tryptophan metabolism in vitamin B6-deficient mice. Br J Nutr 63:27–36

    CAS  PubMed  Google Scholar 

  • Bernassola F, Federıcı M, Corazzarı M, Terrınonı A, Hrıbal ML, de Laurenzı V, Ranallı M, Massa O, Sestı G, Mclean WH, Cıtro G, Barbettı F, Melıno G (2002) Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. FASEB J 16:1371–1378

    CAS  PubMed  Google Scholar 

  • Boden G, Chen X (1995) Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. J Clin Invest 96:1261–1268

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bonnefond A, Clement N, Fawcett K, Yengo L, Vaıllant E, Guıllaume JL, Dechaume A, Payne F, Roussel R, Czernıchow S, Hercberg S, Hadjadj S, Balkau B, Marre M, Lantıerı O, Langenberg C, Bouatıa-Najı N, Charpentıer G, Vaxıllaıre M, Rocheleau G, Wareham NJ, Sladek R, Mccarthy MI, Dına C, Barroso I, Jockers R, Froguel P (2012) Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet 44:297–301

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brandacher G, Wınkler C, Aıgner F, Schwelberger H, Schroecksnadel K, Margreıter R, Fuchs D, Weıss HG (2006) Bariatric surgery cannot prevent tryptophan depletion due to chronic immune activation in morbidly obese patients. Obes Surg 16:541–548

    PubMed  Google Scholar 

  • Brandacher G, Hoeller E, Fuchs D, Weıss HG (2007) Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab 8:289–295

    CAS  PubMed  Google Scholar 

  • Brunıng JC, Gautam D, Burks DJ, Gıllette J, Schubert M, Orban PC, Kleın R, Krone W, Muller-Wıeland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289:2122–2125

    PubMed  Google Scholar 

  • Carl GF, Hoffman WH, Blankenshıp PR, Lıtaker MS, Hoffman MG, Mabe PA (2002) Diabetic ketoacidosis depletes plasma tryptophan. Endocr Res 28:91–102

    CAS  PubMed  Google Scholar 

  • Carter JS, Pugh JA, Monterrosa A (1996) Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med 125:221–232

    CAS  PubMed  Google Scholar 

  • Chen X, Margolıs KJ, Gershon MD, Schwartz GJ, Sze JY (2012) Reduced serotonin reuptake transporter (SERT) function causes insulin resistance and hepatic steatosis independent of food intake. PLoS ONE 7:e32511

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chetyrkın SV, Mathıs ME, Ham AJ, Hachey DL, Hudson BG, Vozıyan PA (2008) Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine. Free Radic Biol Med 44:1276–1285

    PubMed  Google Scholar 

  • Chıarugı A, Rapızzı E, Moronı F (1999) The kynurenine metabolic pathway in the eye: studies on 3-hydroxykynurenine, a putative cataractogenic compound. FEBS Lett 453:197–200

    PubMed  Google Scholar 

  • Claustrat B, Brun J, Chazot G (2005) The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9:11–24

    PubMed  Google Scholar 

  • Concannon P, Rıch SS, Nepom GT (2009) Genetics of type 1A diabetes. N Engl J Med 360:1646–1654

    CAS  PubMed  Google Scholar 

  • Crandall EA, Gıllıs MA, Fernstrom JD (1981) Reduction in brain serotonin synthesis rate in streptozotocin-diabetic rats. Endocrinology 109:310–312

    CAS  PubMed  Google Scholar 

  • Dang Y, Dale WE, Brown OR (2000) Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway. Free Radic Biol Med 28:615–624

    CAS  PubMed  Google Scholar 

  • Davıes JL, Kawaguchı Y, Bennett ST, Copeman JB, Cordell HJ, Prıtchard LE, Reed PW, Gough SC, Jenkıns SC, Palmer SM et al (1994) A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371:130–136

    PubMed  Google Scholar 

  • De Rekeneıre N, Peıla R, Dıng J, Colbert LH, Vısser M, Shorr RI, Krıtchevsky SB, Kuller LH, Strotmeyer ES, Schwartz AV, Vellas B, Harrıs TB (2006) Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 29:1902–1908

    PubMed  Google Scholar 

  • Defronzo RA, Ferrannını E (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173–194

    CAS  PubMed  Google Scholar 

  • Delovıtch TL, Sıngh B (1997) The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity 7:727–738

    PubMed  Google Scholar 

  • Dıaz B, Blazquez E (1986) Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat. Horm Metab Res 18:225–229

    PubMed  Google Scholar 

  • Eastman CL, Guılarte TR (1990) The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine. Neurochem Res 15:1101–1107

    CAS  PubMed  Google Scholar 

  • Egashıra Y, Nakazawa A, Ohta T, Shıbata K, Sanada H (1995) Effect of dietary linoleic acid on the tryptophan-niacin metabolism in streptozotocin diabetic rats. Comp Biochem Physiol A Physiol 111:539–545

    PubMed  Google Scholar 

  • Ekholm R, Erıcson LE, Lundquıst I (1971) Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7:339–348

    CAS  PubMed  Google Scholar 

  • Fernstrom JD (2013) Large neutral amino acids: dietary effects on brain neurochemistry and function. Amino Acids 45:419–430

    CAS  PubMed  Google Scholar 

  • Fıerabraccı V, Novellı M, Cıccarone AM, Masıello P, Benzı L, Navalesı R, Bergamını E (1996) Effects of tryptophan load on amino acid metabolism in type 1 diabetic patients. Diabetes Metab 22:51–56

    PubMed  Google Scholar 

  • Fınkelsteın JA, Chance WT, Fıscher JE (1982) Brain serotonergic activity and plasma amino acid levels in genetically obese Zucker rats. Pharmacol Biochem Behav 17:939–944

    PubMed  Google Scholar 

  • Frıedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770

    PubMed  Google Scholar 

  • Gal EM, Sherman AD (1980) L-kynurenine: its synthesis and possible regulatory function in brain. Neurochem Res 5:223–239

    CAS  PubMed  Google Scholar 

  • Gautron L, Elmquıst JK (2011) Sixteen years and counting: an update on leptin in energy balance. J Clin Invest 121:2087–2093

    PubMed Central  CAS  PubMed  Google Scholar 

  • Genuth S, Albertı KG, Bennett P, Buse J, Defronzo R, Kahn R, Kıtzmıller J, Knowler WC, Lebovıtz H, Lernmark A, Nathan D, Palmer J, Rızza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomılehto J, Zımmet P (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167

    PubMed  Google Scholar 

  • Grohmann U, Fallarıno F, Bıanchı R, Orabona C, Vacca C, Fıorettı MC, Puccettı P (2003) A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. J Exp Med 198:153–160

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hajduch E, Rencurel F, Balendran A, Batty IH, Downes CP, Hundal HS (1999) Serotonin (5-Hydroxytryptamine), a novel regulator of glucose transport in rat skeletal muscle. J Biol Chem 274:13563–13568

    CAS  PubMed  Google Scholar 

  • Hamblın M, Frıedman DB, Hıll S, Caprıolı RM, Smıth HM, Hıll MF (2007) Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. J Mol Cell Cardiol 42:884–895

    PubMed Central  PubMed  Google Scholar 

  • Hattorı M, Kotake Y (1984) Studies on the urinary excretion of xanthurenic acid in diabetics. Acta Vitaminol Enzymol 6:221–228

    PubMed  Google Scholar 

  • Henry RR, Scheaffer L, Olefsky JM (1985) Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 61:917–925

    CAS  PubMed  Google Scholar 

  • Herrera R, Manjarrez G, Nıshımura E, Hernandez J (2003) Serotonin-related tryptophan in children with insulin-dependent diabetes. Pediatr Neurol 28:20–23

    PubMed  Google Scholar 

  • Herrera R, Manjarrez G, Hernandez J (2005) Inhibition and kinetic changes of brain tryptophan-5-hydroxylase during insulin-dependent diabetes mellitus in the rat. Nutr Neurosci 8:57–62

    CAS  PubMed  Google Scholar 

  • Heyes MP, Brew BJ, Martın A, Prıce RW, Salazar AM, Sıdtıs JJ, Yergey JA, Mouradıan MM, Sadler AE, Keılp J et al (1991) Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 29:202–209

    CAS  PubMed  Google Scholar 

  • Hıkıchı T, Tateda N, Mıura T (2011) Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy. Clin Ophthalmol 5:655–660

    PubMed Central  PubMed  Google Scholar 

  • Hırayama A, Nakashıma E, Sugımoto M, Akıyama S, Sato W, Maruyama S, Matsuo S, Tomıta M, Yuzawa Y, Soga T (2012) Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. Anal Bioanal Chem 404:3101–3109

    PubMed  Google Scholar 

  • Hosseını-Tabatabaeı A, Jalılı RB, Lı Y, Kılanı RT, Moeen Rezakhanlou A, Ghahary A (2012) Mechanism underlying defective interferon gamma-induced IDO expression in non-obese diabetic mouse fibroblasts. PLoS ONE 7:e37747

    PubMed Central  PubMed  Google Scholar 

  • Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867

    CAS  PubMed  Google Scholar 

  • Hotamıslıgıl GS, Shargıll NS, Spıegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    PubMed  Google Scholar 

  • Hundley JM, Mcdanıel EG, Sebrell WH (1956) Tryptophan-niacin metabolism in alloxan diabetic rats. J Nutr 59:407–423

    CAS  PubMed  Google Scholar 

  • Hurley JH, Zhang S, Bye LS, Marshall MS, Depaolı-Roach AA, Guan K, Fox AP, Yu L (2003) Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase. BMC Neurosci 4:10

    PubMed Central  PubMed  Google Scholar 

  • Jain SK (2008) Can tryptophan oxidation lead to lower tryptophan level in diabetes? A commentary on “Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine”. Free Radic Biol Med 44:1273–1275

    CAS  PubMed  Google Scholar 

  • Jalılı RB, Forouzandeh F, Rezakhanlou AM, Hartwell R, Medına A, Warnock GL, Larıjanı B, Ghahary A (2010) Local expression of indoleamine 2,3 dioxygenase in syngeneic fibroblasts significantly prolongs survival of an engineered three-dimensional islet allograft. Diabetes 59:2219–2227

    PubMed Central  PubMed  Google Scholar 

  • Kadowakı T, Yamauchı T, Kubota N, Hara K, Uekı K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792

    PubMed Central  PubMed  Google Scholar 

  • Kanth VR, Lavanya K, Srınıvas J, Raju TN (2009) Elevated Expression of indoleamine 2,3-dioxygenase (IDO) and accumulation of kynurenic acid in the pathogenesis of STZ-induced diabetic cataract in Wistar rats. Curr Eye Res 34:274–281

    CAS  PubMed  Google Scholar 

  • Karamıtrı A, Renault N, Clement N, Guıllaume JL, Jockers R (2013) Minireview: toward the establishment of a link between melatonin and glucose homeostasis: association of melatonin MT2 receptor variants with type 2 diabetes. Mol Endocrinol 27:1217–1233

    PubMed  Google Scholar 

  • Kıeffer TJ, Habener JF (2000) The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 278:E1–E14

    PubMed  Google Scholar 

  • Kleın BE, Kleın R, Moss SE, Cruıckshanks KJ (1996) Parental history of diabetes in a population-based study. Diabetes Care 19:827–830

    PubMed  Google Scholar 

  • Ko IY, Jun HS, Kım GS, Yoon JW (1994) Studies on autoimmunity for initiation of beta-cell destruction. X. Delayed expression of a membrane-bound islet cell-specific 38 kDa autoantigen that precedes insulitis and diabetes in the diabetes-prone BB rat. Diabetologia 37:460–465

    CAS  PubMed  Google Scholar 

  • Koenıg P, Nagl C, Neurauter G, Schennach H, Brandacher G, Fuchs D (2010) Enhanced degradation of tryptophan in patients on hemodialysis. Clin Nephrol 74:465–470

    PubMed  Google Scholar 

  • Kolb H (1987) Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice. Diabetes Metab Rev 3:751–778

    CAS  PubMed  Google Scholar 

  • Kosa E, Maurel D, Sıaud P (2001) Effects of pinealectomy on glucagon responsiveness to hypoglycaemia induced by insulin injections in fed rats. Exp Physiol 86:617–620

    CAS  PubMed  Google Scholar 

  • Kotake Y, Ueda T, Morı T, Igakı S, Hattorı M (1975) Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA). Acta Vitaminol Enzymol 29:236–239

    CAS  PubMed  Google Scholar 

  • Lackovıc Z, Salkovıc M (1990) Streptozotocin and alloxan produce alterations in rat brain monoamines independently of pancreatic beta cells destruction. Life Sci 46:49–54

    PubMed  Google Scholar 

  • Larrea E, Rıezu-Boj JI, Gıl-Guerrero L, Casares N, Aldabe R, Sarobe P, Cıveıra MP, Heeney JL, Rollıer C, Verstrepen B, Wakıta T, Borras-Cuesta F, Lasarte JJ, Prıeto J (2007) Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection. J Virol 81:3662–3666

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lauro D, Kıdo Y, Castle AL, Zarnowskı MJ, Hayashı H, Ebına Y, Accılı D (1998) Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue. Nat Genet 20:294–298

    CAS  PubMed  Google Scholar 

  • Lellı SM, Mazzettı MB, San Martın de Vıale LC (2008) Hepatic alteration of tryptophan metabolism in an acute porphyria model Its relation with gluconeogenic blockage. Biochem Pharmacol 75:704–712

    PubMed  Google Scholar 

  • Lı X, Zhang M, Tang W (2013) Effects of melatonin on streptozotocin-induced retina neuronal apoptosis in high blood glucose rat. Neurochem Res 38:669–676

    PubMed  Google Scholar 

  • Macchıarulo A, Camaıonı E, Nutı R, Pellıccıarı R (2009) Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease. Amino Acids 37:219–229

    PubMed  Google Scholar 

  • Malına HZ, Rıchter C, Mehl M, Hess OM (2001) Pathological apoptosis by xanthurenic acid, a tryptophan metabolite: activation of cell caspases but not cytoskeleton breakdown. BMC Physiol 1:7

    PubMed Central  PubMed  Google Scholar 

  • Marston OJ, Garfıeld AS, Heısler LK (2011) Role of central serotonin and melanocortin systems in the control of energy balance. Eur J Pharmacol 660:70–79

    CAS  PubMed  Google Scholar 

  • Martın S, Wolf-Eıchbaum D, Duınkerken G, Scherbaum WA, Kolb H, Noordzıj JG, Roep BO (2001) Development of type 1 diabetes despite severe hereditary B-lymphocyte deficiency. N Engl J Med 345:1036–1040

    PubMed  Google Scholar 

  • Masıello P, Balestrerı E, Baccıola D, Bergamını E (1987) Influence of experimental diabetes on brain levels of monoamine neurotransmitters and their precursor amino acids during tryptophan loading. Acta Diabetol Lat 24:43–50

    PubMed  Google Scholar 

  • Mcmullan CJ, Schernhammer ES, Rımm EB, Hu FB, Forman JP (2013) Melatonin secretion and the incidence of type 2 diabetes. JAMA 309:1388–1396

    PubMed Central  CAS  PubMed  Google Scholar 

  • Melchıor D, Le Floc’h N, Seve B (2003) Effects of chronic lung inflammation on tryptophan metabolism in piglets. Adv Exp Med Biol 527:359–362

    PubMed  Google Scholar 

  • Meyramov G, Korchın V, Kocheryzkına N (1998) Diabetogenic activity of xanthurenic acid determined by its chelating properties? Transplant Proc 30:2682–2684

    CAS  PubMed  Google Scholar 

  • Moller DE, Flıer JS (1991) Insulin resistance–mechanisms, syndromes, and implications. N Engl J Med 325:938–948

    CAS  PubMed  Google Scholar 

  • Moore MC, Kımura K, Shıbata H, Honjoh T, Saıto M, Everett CA, Smıth MS, Cherrıngton AD (2005) Portal 5-hydroxytryptophan infusion enhances glucose disposal in conscious dogs. Am J Physiol Endocrinol Metab 289:E225–E231

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moran A, Zhang HJ, Olson LK, Harmon JS, Poıtout V, Robertson RP (1997) Differentiation of glucose toxicity from beta cell exhaustion during the evolution of defective insulin gene expression in the pancreatic islet cell line, HIT-T15. J Clin Invest 99:534–539

    PubMed Central  CAS  PubMed  Google Scholar 

  • Morıoka T, Asılmaz E, Hu J, Dıshınger JF, Kurpad AJ, Elıas CF, Lı H, Elmquıst JK, Kennedy RT, Kulkarnı RN (2007) Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice. J Clin Invest 117:2860–2868

    PubMed Central  PubMed  Google Scholar 

  • Munıpally PK, Agraharm SG, Valavala VK, Gundae S, Turlapatı NR (2011) Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients. Arch Physiol Biochem 117:254–258

    PubMed  Google Scholar 

  • Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193

    CAS  PubMed  Google Scholar 

  • Murakoshı M, Tanımoto M, Gohda T, Hagıwara S, Ohara I, Toyoda H, Ishıkawa Y, Horıkoshı S, Tomıno Y (2009) Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice. Diabetes Res Clin Pract 83:183–189

    PubMed  Google Scholar 

  • Nakayama M, Abıru N, Morıyama H, Babaya N, Lıu E, Mıao D, Yu L, Wegmann DR, Hutton JC, Ellıott JF, Eısenbarth GS (2005) Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 435:220–223

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nıınısalo P, Raıtala A, Pertovaara M, Oja SS, Lehtımakı T, Kahonen M, Reunanen A, Jula A, Moılanen L, Kesanıemı YA, Nıemınen MS, Hurme M (2008) Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study. Scand J Clin Lab Invest 68:767–770

    PubMed  Google Scholar 

  • Nıshıda S, Sato R, Muraı I, Nakagawa S (2003) Effect of pinealectomy on plasma levels of insulin and leptin and on hepatic lipids in type 2 diabetic rats. J Pineal Res 35:251–256

    PubMed  Google Scholar 

  • Nıtta T, Murata S, Ueno T, Tanaka K, Takahama Y (2008) Thymic microenvironments for T-cell repertoire formation. Adv Immunol 99:59–94

    PubMed  Google Scholar 

  • Nonogakı K, Strack AM, Dallman MF, Tecott LH (1998) Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 4:1152–1156

    PubMed  Google Scholar 

  • Noto Y, Okamoto H (1978) Inhibition by kynurenine metabolites of proinsulin synthesis in isolated pancreatic islets. Acta Diabetol Lat 15:273–282

    CAS  PubMed  Google Scholar 

  • Ohtsubo K, Takamatsu S, Mınowa MT, Yoshıda A, Takeuchı M, Marth JD (2005) Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell 123:1307–1321

    CAS  PubMed  Google Scholar 

  • Okamoto H (2003) Recent advances in physiological and pathological significance of tryptophan-NAD+ metabolites: lessons from insulin-producing pancreatic beta-cells. Adv Exp Med Biol 527:243–252

    CAS  PubMed  Google Scholar 

  • Orosco M, Rouch C, Gerozıssıs K (2000) Activation of hypothalamic insulin by serotonin is the primary event of the insulin-serotonin interaction involved in the control of feeding. Brain Res 872:64–70

    CAS  PubMed  Google Scholar 

  • Oxenkrug GF (2007) Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging. Ann N Y Acad Sci 1122:35–49

    CAS  PubMed  Google Scholar 

  • Oxenkrug GF (2010a) Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism. Ann N Y Acad Sci 1199:1–14

    CAS  PubMed  Google Scholar 

  • Oxenkrug GF (2010b) Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later. Isr J Psychiatry Relat Sci 47:56–63

    PubMed Central  PubMed  Google Scholar 

  • Oxenkrug G (2013) Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol Neurobiol 48:294–301

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oxenkrug GF, Requıntına PJ (2003) Melatonin and jet lag syndrome: experimental model and clinical implications. CNS Spectr 8:139–148

    PubMed  Google Scholar 

  • Oxenkrug GF, Turskı WA, Zgrajka W, Weınstock JV, Summergrad P (2013) Tryptophan-kynurenine metabolism and insulin resistance in hepatitis C patients. Hepat Res Treat 2013:149247

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pandı-Perumal SR, Trakht I, Srınıvasan V, Spence DW, Maestronı GJ, Zısapel N, Cardınalı DP (2008) Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85:335–353

    PubMed  Google Scholar 

  • Paolısso G, Tatarannı PA, Foley JE, Bogardus C, Howard BV, Ravussın E (1995) A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38:1213–1217

    PubMed  Google Scholar 

  • Papazoglou I, Berthou F, Vıcaıre N, Rouch C, Markakı EM, Baılbe D, Portha B, Taouıs M, Gerozıssıs K (2012) Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model. Mol Cell Endocrinol 350:136–144

    CAS  PubMed  Google Scholar 

  • Patterson AD, Bonzo JA, Lı F, Krausz KW, Eıchler GS, Aslam S, Tıgno X, Weınsteın JN, Hansen BC, Idle JR, Gonzalez FJ (2011) Metabolomics reveals attenuation of the SLC6A20 kidney transporter in nonhuman primate and mouse models of type 2 diabetes mellitus. J Biol Chem 286:19511–19522

    PubMed Central  CAS  PubMed  Google Scholar 

  • Paulmann N, Grohmann M, Voıgt JP, Bert B, Vowınckel J, Bader M, Skelın M, Jevsek M, Fınk H, Rupnık M, Walther DJ (2009) Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol 7:e1000229

    PubMed Central  PubMed  Google Scholar 

  • Pawlak K, Domanıewskı T, Myslıwıec M, Pawlak D (2009) The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease. Atherosclerosis 204:309–314

    CAS  PubMed  Google Scholar 

  • Pertovaara M, Raıtala A, Juonala M, Lehtımakı T, Huhtala H, Oja SS, Jokınen E, Vııkarı JS, Raıtakarı OT, Hurme M (2007) Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study. Clin Exp Immunol 148:106–111

    PubMed Central  CAS  PubMed  Google Scholar 

  • Peschke E, Frese T, Chankıewıtz E, Peschke D, Preıss U, Schneyer U, Spessert R, Muhlbauer E (2006) 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 40:135–143

    CAS  PubMed  Google Scholar 

  • Petersen KF, Dufour S, Befroy D, Garcıa R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pıcınato MC, Haber EP, Carpınellı AR, Cıpolla-Neto J (2002) Daily rhythm of glucose-induced insulin secretion by isolated islets from intact and pinealectomized rat. J Pineal Res 33:172–177

    PubMed  Google Scholar 

  • Polychronakos C, Lı Q (2011) Understanding type 1 diabetes through genetics: advances and prospects. Nat Rev Genet 12:781–792

    CAS  PubMed  Google Scholar 

  • Puglıese A, Zeller M, JR. Fernandez A, Zalcberg LJ, Bartlett RJ, Rıcordı C, Pıetropaolo M, Eısenbarth GS, Bennett ST, Patel DD (1997) The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 15:293–297

    PubMed  Google Scholar 

  • Pulımeno P, Mannıc T, Sage D, Gıovannonı L, Salmon P, Lemeılle S, Gıry-Laterrıere M, Unser M, Bosco D, Bauer C, Morf J, Halban P, Phılıppe J, Dıbner C (2013) Autonomous and self-sustained circadian oscillators displayed in human islet cells. Diabetologia 56:497–507

    PubMed Central  PubMed  Google Scholar 

  • Radzıuk J, Pye S (2006) Diurnal rhythm in endogenous glucose production is a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour? Diabetologia 49:1619–1628

    PubMed  Google Scholar 

  • Raju TN, Kanth VR, Reddy PU (2007) Influence of kynurenines in pathogenesis of cataract formation in tryptophan-deficient regimen in Wistar rats. Indian J Exp Biol 45:543–548

    CAS  PubMed  Google Scholar 

  • Redondo MJ, Rewers M, Yu L, Garg S, Pılcher CC, Ellıott RB, Eısenbarth GS (1999) Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study. BMJ 318:698–702

    PubMed Central  CAS  PubMed  Google Scholar 

  • Reılly JG, Mctavısh SF, Young AH (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. J Psychopharmacol 11:381–392

    PubMed  Google Scholar 

  • Rıchmond JE, Codıgnola A, Cooke IM, Sher E (1996) Calcium- and barium-dependent exocytosis from the rat insulinoma cell line RINm5F assayed using membrane capacitance measurements and serotonin release. Pflugers Arch 432:258–269

    PubMed  Google Scholar 

  • Robınson CM, Hale PT, Carlın JM (2005) The role of IFN-gamma and TNF-alpha-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase. J Interferon Cytokine Res 25:20–30

    PubMed Central  PubMed  Google Scholar 

  • Robotka H, Sas K, Agoston M, Rozsa E, Szenası G, Gıgler G, Vecseı L, Toldı J (2008) Neuroprotection achieved in the ischaemic rat cortex with L-kynurenine sulphate. Life Sci 82:915–919

    CAS  PubMed  Google Scholar 

  • Rodrıguez V, Mellado C, Alvarez E, DE Dıego JG, Blazquez E (1989) Effect of pinealectomy on liver insulin and glucagon receptor concentrations in the rat. J Pineal Res 6:77–88

    PubMed  Google Scholar 

  • Rogers KS, Evangelısta SJ (1985) 3-Hydroxykynurenine, 3-hydroxyanthranilic acid, and o-aminophenol inhibit leucine-stimulated insulin release from rat pancreatic islets. Proc Soc Exp Biol Med 178:275–278

    CAS  PubMed  Google Scholar 

  • Romero-Gomez M (2006) Insulin resistance and hepatitis C. World J Gastroenterol 12:7075–7080

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rongvaux A, Andrıs F, van Gool F, Leo O (2003) Reconstructing eukaryotic NAD metabolism. Bioessays 25:683–690

    CAS  PubMed  Google Scholar 

  • Rosen DA, Maengwyn-Davıes GD, Becker B, Stone HH, Frıedenwald JS (1955) Xanthurenic acid excretion studies in diabetics with and without retinopathy. Proc Soc Exp Biol Med 88:321–323

    CAS  PubMed  Google Scholar 

  • Rothe H, Jenkıns NA, Copeland NG, Kolb H (1997) Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2. J Clin Invest 99:469–474

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rothman DL, Magnusson I, Clıne G, Gerard D, Kahn CR, Shulman RG, Shulman GI (1995) Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 92:983–987

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rowe RE, Leech NJ, Nepom GT, Mcculloch DK (1994) High genetic risk for IDDM in the Pacific Northwest. First report from the Washington State Diabetes Prediction Study. Diabetes 43:87–94

    CAS  PubMed  Google Scholar 

  • Rozsa E, Robotka H, Nagy D, Farkas T, Sas K, Vecseı L, Toldı J (2008) The pentylenetetrazole-induced activity in the hippocampus can be inhibited by the conversion of L-kynurenine to kynurenic acid: an in vitro study. Brain Res Bull 76:474–479

    CAS  PubMed  Google Scholar 

  • Sakowskı SA, Geddes TJ, Thomas DM, Levı E, Hatfıeld JS, Kuhn DM (2006) Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies. Brain Res 1085:11–18

    PubMed  Google Scholar 

  • Salıdo EM, Bordone M, de Laurentııs A, Chıanellı M, Keller Sarmıento MI, Dorfman D, Rosensteın RE (2013) Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats. J Pineal Res 54:179–189

    PubMed  Google Scholar 

  • Santın I, Eızırık DL (2013) Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and beta-cell apoptosis. Diabetes Obes Metab 15(Suppl 3):71–81

    PubMed  Google Scholar 

  • Sartorı C, Dessen P, Mathıeu C, Monney A, Bloch J, Nıcod P, Scherrer U, Duplaın H (2009) Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology 150:5311–5317

    PubMed  Google Scholar 

  • Sasakı N, Egashıra Y, Sanada H (2009) Production of L-tryptophan-derived catabolites in hepatocytes from streptozotocin-induced diabetic rats. Eur J Nutr 48:145–153

    PubMed  Google Scholar 

  • Scheer FA, Hılton MF, Mantzoros CS, Shea SA (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A 106:4453–4458

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schulz LO, Bennett PH, Ravussın E, Kıdd JR, Kıdd KK, Esparza J, Valencıa ME (2006) Effects of traditional and western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S. Diabetes Care 29:1866–1871

    PubMed  Google Scholar 

  • Schwarcz R, Pellıccıarı R (2002) Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther 303:1–10

    CAS  PubMed  Google Scholar 

  • Sıngh M, Jadhav HR (2014) Melatonin: functions and ligands. Drug Discov Today 19(9):1410–1418

    PubMed  Google Scholar 

  • Sladek R, Rocheleau G, Rung J, Dına C, Shen L, Serre D, Boutın P, Vıncent D, Belısle A, Hadjadj S, Balkau B, Heude B, Charpentıer G, Hudson TJ, Montpetıt A, Pshezhetsky AV, Prentkı M, Posner BI, Baldıng DJ, Meyre D, Polychronakos C, Froguel P (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885

    CAS  PubMed  Google Scholar 

  • Smıth PA, Proks P, Ashcroft FM (1999) Quantal analysis of 5-hydroxytryptamine release from mouse pancreatic beta-cells. J Physiol 521(Pt 3):651–664

    PubMed Central  PubMed  Google Scholar 

  • Sullıvan PW, Morrato EH, Ghushchyan V, Wyatt HR, Hıll JO (2005) Obesity, inactivity, and the prevalence of diabetes and diabetes-related cardiovascular comorbidities in the U.S., 2000–2002. Diabetes Care 28:1599–1603

    PubMed  Google Scholar 

  • Tabak AG, Jokela M, Akbaraly TN, Brunner EJ, Kıvımakı M, Wıtte DR (2009) Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373:2215–2221

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tanabe A, Egashıra Y, Fukuoka S, Shıbata K, Sanada H (2002) Expression of rat hepatic 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase is affected by a high protein diet and by streptozotocin-induced diabetes. J Nutr 132:1153–1159

    CAS  PubMed  Google Scholar 

  • Tecott LH (2007) Serotonin and the orchestration of energy balance. Cell Metab 6:352–361

    CAS  PubMed  Google Scholar 

  • Tısch R, Mcdevıtt H (1996) Insulin-dependent diabetes mellitus. Cell 85:291–297

    PubMed  Google Scholar 

  • Trulson ME, Jacoby JH, Mackenzıe RG (1986) Streptozotocin-induced diabetes reduces brain serotonin synthesis in rats. J Neurochem 46:1068–1072

    CAS  PubMed  Google Scholar 

  • Tutuncu NB, Batur MK, Yıldırır A, Tutuncu T, Deger A, Koray Z, Erbas B, Kabakcı G, Aksoyek S, Erbas T (2005) Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy. J Pineal Res 39:43–49

    CAS  PubMed  Google Scholar 

  • Uysal KT, Wıesbrock SM, Marıno MW, Hotamıslıgıl GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614

    CAS  PubMed  Google Scholar 

  • Vafıadıs P, Ounıssı-Benkalha H, Palumbo M, Grabs R, Rousseau M, Goodyer CG, Polychronakos C (2001) Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes. J Clin Endocrinol Metab 86:3705–3710

    PubMed  Google Scholar 

  • van de Kamp JL, Smolen A (1995) Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6. Pharmacol Biochem Behav 51:753–758

    PubMed  Google Scholar 

  • van Heyningen R (1971) Fluorescent glucoside in the human lens. Nature 230:393–394

    PubMed  Google Scholar 

  • Verge CF, Gıananı R, Kawasakı E, Yu L, Pıetropaolo M, Jackson RA, Chase HP, Eısenbarth GS (1996) Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45:926–933

    CAS  PubMed  Google Scholar 

  • Voıght BF, Scott LJ, Steınthorsdottır V, Morrıs AP, Dına C, Welch RP, Zeggını E, Huth C, Aulchenko YS, Thorleıfsson G, Mcculloch LJ, Ferreıra T, Grallert H, Amın N, Wu G, Wıller CJ, Raychaudhurı S, Mccarroll SA, Langenberg C, Hofmann OM, Dupuıs J, Qı L, Segre AV, Van Hoek M, Navarro P, Ardlıe K, Balkau B, Benedıktsson R, Bennett AJ, Blagıeva R, Boerwınkle E, Bonnycastle LL, Bengtsson Bostrom K, Bravenboer B, Bumpstead S, Burtt NP, Charpentıer G, Chınes PS, Cornelıs M, Couper DJ, Crawford G, Doney AS, Ellıott KS, Ellıott AL, Erdos MR, Fox CS, Franklın CS, Ganser M, Gıeger C, Grarup N, Green T, Grıffın S, Groves CJ, Guıduccı C, Hadjadj S, Hassanalı N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jorgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusısto J, Laurıtzen T, Lı M, Lıeverse A, Lındgren CM, Lyssenko V, Marre M, Meıtınger T, Mıdthjell K, Morken MA, Narısu N, Nılsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proenca C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shıelds BM, Shrader P, Sıgurdsson G, Sparso T, Strassburger K, Strıngham HM, Sun Q, Swıft AJ, Thorand B et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579–589

    PubMed Central  PubMed  Google Scholar 

  • Wade JM, Juneja P, Mackay AW, Graham J, Havel PJ, Tecott LH, Gouldıng EH (2008) Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. Endocrinology 149:955–961

    PubMed Central  CAS  PubMed  Google Scholar 

  • Walther DJ, Peter JU, Wınter S, Holtje M, Paulmann N, Grohmann M, Vowınckel J, Alamo-Bethencourt V, Wılhelm CS, Ahnert-Hılger G, Bader M (2003) Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell 115:851–862

    CAS  PubMed  Google Scholar 

  • Weıgle DS, Duell PB, Connor WE, Steıner RA, Soules MR, Kuıjper JL (1997) Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 82:561–565

    PubMed  Google Scholar 

  • Wırleıtner B, Rudzıte V, Neurauter G, Murr C, Kalnıns U, Erglıs A, Trusınskıs K, Fuchs D (2003) Immune activation and degradation of tryptophan in coronary heart disease. Eur J Clin Invest 33:550–554

    PubMed  Google Scholar 

  • Wolowczuk I, Hennart B, Leloıre A, Bessede A, Soıchot M, Taront S, Caıazzo R, Raverdy V, Pıgeyre M, Guıllemın GJ, Allorge D, Pattou F, Froguel P, Poulaın-Godefroy O (2012) Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone. Am J Physiol Regul Integr Comp Physiol 303:R135–R143

    CAS  PubMed  Google Scholar 

  • Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17

    PubMed  Google Scholar 

  • Yadav VK, Oury F, Suda N, Lıu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gıngrıch JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976–989

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yamada J, Sugımoto Y, Ujıkawa M (2006) Involvement of leptin in hypophagia induced by the serotonin precursor 5-hydroxytryptophan (5-HTP) in mice. Biol Pharm Bull 29:557–559

    CAS  PubMed  Google Scholar 

  • Yang YF, Lın MT (1995) Brain serotonin depletion attenuates diabetogenic effects of streptozotocin. Am J Physiol 268:E839–E844

    CAS  PubMed  Google Scholar 

  • Yang M, Charlton B, Gautam AM (1997) Development of insulitis and diabetes in B cell-deficient NOD mice. J Autoimmun 10:257–260

    CAS  PubMed  Google Scholar 

  • Yasuı H, Takaı K, Yoshıda R, Hayaıshı O (1986) Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients. Proc Natl Acad Sci U S A 83:6622–6626

    PubMed Central  PubMed  Google Scholar 

  • Zarnowskı T, Rejdak R, Zıelınska-Rzecka E, Zrenner E, Grıeb P, Zagorskı Z, Junemann A, Turskı WA (2007) Elevated concentrations of kynurenic acid, a tryptophan derivative, in dense nuclear cataracts. Curr Eye Res 32:27–32

    PubMed  Google Scholar 

  • Zeggını E, Scott LJ, Saxena R, Voıght BF, Marchını JL, Hu T, De Bakker PI, Abecasıs GR, Almgren P, Andersen G, Ardlıe K, Bostrom KB, Bergman RN, Bonnycastle LL, Borch-Johnsen K, Burtt NP, Chen H, Chınes PS, Daly MJ, Deodhar P, Dıng CJ, Doney AS, Duren WL, Ellıott KS, Erdos MR, Fraylıng TM, Freathy RM, Gıannıny L, Grallert H, Grarup N, Groves CJ, Guıduccı C, Hansen T, Herder C, Hıtman GA, Hughes TE, Isomaa B, Jackson AU, Jorgensen T, Kong A, Kubalanza K, Kuruvılla FG, Kuusısto J, Langenberg C, Lango H, Laurıtzen T, Lı Y, Lındgren CM, Lyssenko V, Marvelle AF, Meısınger C, Mıdthjell K, Mohlke KL, Morken MA, Morrıs AD, Narısu N, Nılsson P, Owen KR, Palmer CN, Payne F, Perry JR, Pettersen E, Platou C, Prokopenko I, Qı L, Qın L, Rayner NW, Rees M, Roıx JJ, Sandbaek A, Shıelds B, Sjogren M, Steınthorsdottır V, Strıngham HM, Swıft AJ, Thorleıfsson G, Thorsteınsdottır U, Tımpson NJ, Tuomı T, Tuomılehto J, Walker M, Watanabe RM, Weedon MN, Wıller CJ, Illıg T, Hveem K, Hu FB, Laakso M, Stefansson K, Pedersen O, Wareham NJ, Barroso I, Hattersley AT, Collıns FS, Groop L, Mccarthy MI, Boehnke M, Altshuler D (2008) Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40:638–645

    PubMed Central  PubMed  Google Scholar 

  • Zhang Y, Proenca R, Maffeı M, Barone M, Leopold L, Frıedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432

    CAS  PubMed  Google Scholar 

  • Zhou L, Sutton GM, Rochford JJ, Semple RK, Lam DD, Oksanen LJ, Thornton-Jones ZD, Clıfton PG, Yueh CY, Evans ML, Mccrımmon RJ, Elmquıst JK, Butler AA, Heısler LK (2007) Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab 6:398–405

    PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Kirklareli State Hospital, Kirklareli, 39020, Turkey

    Ugur Unluturk M.D.

  2. Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Sihhiye, Ankara, Turkey

    Tomris Erbas M.D.

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Correspondence to Tomris Erbas M.D. .

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  1. Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey

    Atilla Engin

  2. Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey

    Ayse Basak Engin

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Unluturk, U., Erbas, T. (2015). Diabetes and Tryptophan Metabolism. In: Engin, A., Engin, A. (eds) Tryptophan Metabolism: Implications for Biological Processes, Health and Disease. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15630-9_7

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