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High Blood Glucose and Damage to Neuronal Tissue

  • Robert R. MillerJr.
Chapter

Abstract

Type-1, type-2, and gestational/embryonic diabetes are all damaging and impair the nervous system. All three forms of diabetes cause oxidative stress, apoptosis, and neuropathy. In type-1 and type-2 diabetes (T2D), oxidative stress and apoptosis involve excessive release of glutamate, activation of N-methyl-d-aspartate (NMDA) receptors, increased cytoplasmic Ca+2 levels, and complex signaling pathways leading to apoptosis. Neuropathy has also been associated with a reduction in a number of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and the use of exogenous BDNF and GDNF in ameliorating type-1 and type-2 diabetic symptoms has been reported. While several regions of the brain are affected, the hypothalamus and hippocampus are key areas of neuropathy. While less understood, gestational diabetes also causes oxidative stress and apoptosis within fetal brains and embryonic hyperglycemia is associated with hyperhomocysteinemia and subsequent apoptosis. Elevated embryonic homocysteine (HoCys) levels promote membrane lipid peroxidation, apoptosis, and are teratogenic in chicks. Data presented in this review indicate that embryonic hyperglycemia inhibits both the remethylation pathway, which is largely dependent on 5-methyltetrahydrofolate levels, and the transsulfuration pathway, which removes HoCys ultimately to α-ketobutyrate, glutathione, and taurine. HoCys is of interest because HoCys is both an agonist and antagonist of NMDA receptors.

Keywords

Gestational Diabetes Membrane Lipid Peroxidation Xanthine Oxidase Activity Taurine Level Transsulfuration Pathway 
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.

Abbreviations

AChE

Acetylcholine esterase

BDNF

Brain-derived neurotrophic factor

ChAT

Choline acetyltransferase

DHA

Docosahexaenoic acid

10-FTHF DH

10-formyltetrahydrofolate dehydrogenase

10-FTHF hydrolase

10-formyltetrahydrofolate hydrolase

GDNF

Glial cell line-derived neurotrophic factor

GFAP

Glial fibrillary acidic protein

GLUTS

Glucose transporters

HoCys

Homocysteine

5-Methyl THF

5-methyltetrahydrofolate

NTDs

Neural tube defects

NMDA

N-methyl-d-aspartate

SAH

S-adenosylhomocysteine

SAM

S-adenosylmethionine

STZ

Streptozocin

TBARS

Thiobarbituric acid reactive substances

T1D

Type-1 diabetes

T2D

Type-2 diabetes

Notes

Acknowledgments

I am very thankful for the superb technical assistance of Ms. Kelly Colesman and Ms. Sarah Yearsley who performed the taurine, 10-FTHF DH, and 10-FTHF hydrolase assays (Tables 173.1 and 173.2; Figs. 173.3, 173.4, 173.5, and 173.6). This article is dedicated to the memories of Grace, Evelyn, and Robert Miller, Sr.

References

  1. Anderson MS, Flowers-Ziegler J, Das UG, Hay WH Jr, Devaskar SU. Am J Regulatory Integrative Comp Physiol. 2001;281:R1545–52.Google Scholar
  2. Anggard E, Samuelsson B. J Biol Chem. 1965;240:3518–21.PubMedGoogle Scholar
  3. Anitha M, Gondha, C, Sutliff R, Parasadanian A, Mwangi S, Sitaraman SV, Srinivasan S. J Clin Invest. 2006;116:344–56.PubMedCrossRefGoogle Scholar
  4. Ashokkumar N, Pari L, Ramkumar K. Basic Clin Pharm Toxicol. 2006;99:246–50.CrossRefGoogle Scholar
  5. Ates O, Cayli SR, Yucel N, Altinoz E, Kocak A, Akif Durak M, Turkoz Y, Yologlu S. J Clin Neuroscience. 2007;14:256–60.CrossRefGoogle Scholar
  6. Barbacid M. Curr Opin Cell Biol. 1995;7:148–55.PubMedCrossRefGoogle Scholar
  7. Barnett RK, Booms, SL, Gura T, Gushrowski M, Miller RR Jr. Comp Biochem Physiol. 2009;150C:107–12.Google Scholar
  8. Bartolomucci A, La Corte G, Possent R, Locatelli V, Rigamonti AE, Torsello A, Bresciani E, Bulgarelli I, Rizzi R, Pavone F, D’Amato FR, Severini, C, Mignogna G, Giorgi A, Schinina ME, Ela G, Brancia C, Ferri G-L, Ciani B, Pascuuci T, Dell’Omo G, Muller EE, Levi A, Moles A. Proc Natl Acad Sci USA. 2006;103:14584–9.PubMedCrossRefGoogle Scholar
  9. Baskin DG, Figleicz DP, Woods SC, Pore DJ, Dorsa DM. Ann Rev Physiol. 1987;49:335–47.CrossRefGoogle Scholar
  10. Beauguis J, Homo-Delarche F, Revsin Y, De Nicola AF, Saravia F. Neuroimmunomodulation 2008;15:61–7.Google Scholar
  11. Becerra JE, Khoury MJ, Cordero, JF, Erickson JD. Pediatrics 85:1–9.Google Scholar
  12. Bemur C, Ste-Marie L, Montogomery J. Neurochem Int. 2007;50:890–904.Google Scholar
  13. Blokland A, Jolies J. Pharmacol Biochem Behav. 1993;44:491–4.PubMedCrossRefGoogle Scholar
  14. Boyles, AL, Billups, AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout AF, George TM, Enterline DS, Gilbert JR, Speer MC. Env Health Perspect. 2006;114:1547–52.CrossRefGoogle Scholar
  15. Brakenhielm E, Cao R, Cao Y. FASEB J. 2001;15:1798–800.PubMedGoogle Scholar
  16. Cabeza R, Prince SE, Daselaar SM, Greenberg DL, Budde M, Dolcos F, Labar KS, Ruben DC. J Cogn Neurosci. 2004;16:1583–94.PubMedCrossRefGoogle Scholar
  17. Carmel R, Jacobson DW, editors. Homocysteine in health and disease. UK: Cambridge University Press; 2001.Google Scholar
  18. Caulfield MP, Birdsall NJM. Pharmacol Rev. 1998;50:270–90.Google Scholar
  19. Chakraborty TR, Tkalych O, Nanno D, Garcia AL, Devi LA, Salton SRJ. Brain Res. 2006;1089:21–32.PubMedCrossRefGoogle Scholar
  20. Chen X-C, Pan Z-L, Liu D-S, Han X. Adv Exp Med Biol. 1998;442:397–403.PubMedGoogle Scholar
  21. Coles NW, Weaver KR, Walcher BN, Adams ZF, Miller RR Jr. Comp Biochem Physiol. 2008;150B:338–43.Google Scholar
  22. Farr SA, Yamada, KA, Butterfield DA, Abdul HM, Xu L, Miller NE, Banks WA, Morley JE. Endocrinology 2008;149:2628–36.PubMedCrossRefGoogle Scholar
  23. Fine EL, Horal M, Chang TI, Fortin G, Locken MR. Diabetes 1999;48:2454–62.PubMedCrossRefGoogle Scholar
  24. Friedlander RM. New Engl J Med. 2009;348:1365–75.CrossRefGoogle Scholar
  25. Gao O, Gao YM. Int J Dev Neurosci. 2007;25:349–357.Google Scholar
  26. Gautam D, Gavrilova O, Jeon J, Pack S, Jou W, Cui Y, Li JH, Wess J. Cell Metab. 2006;4:363–75.PubMedCrossRefGoogle Scholar
  27. Gautam D, Jeon J, Starost MF, Han S-J, Hamdan FF, Cui Y, Parlow AF, Gavrilova O, Szalayova I, Mezey E, Wess J. Proc Natl Acad Sci USA. 2009;106:6398–403.PubMedCrossRefGoogle Scholar
  28. Ghareeb DA, Hussen HM. Neurosci Lett. 2008;436:44–7.PubMedCrossRefGoogle Scholar
  29. Goldman AS, Baker L, Piddington R, Marx B, Herold R, Egler J. Proc Natl Acad Sci USA. 1985;82:8227–31.PubMedCrossRefGoogle Scholar
  30. Gonzalez-Zulueta M, Ensz, Mukhina G, Lebrovitz RM, Zwacka RM, Engelhardt JF, Oberly LW, Dawson LW, Dawson VL, Dawson TM. J Neurosci. 1998;15:2040–55.Google Scholar
  31. Guo C, Quobatari A, Shangguan Y, Hong S, Wiley JW. Neurogastroenterol Motil. 2004;16:355–45.CrossRefGoogle Scholar
  32. Hahm S, Mizuno TM, Wu J, Wisor JP, Priest, CA, Kozak CA, Boozer CN, Peng B, McEvoy RC, Good P, Kelley KA, Takahashi JS, Pintar JE, Roberts, JL, Mobbs CV, Salton SRJ. Neuron 1999;537–48.Google Scholar
  33. Hamburger V, Hamilton HL. J Morphol. 1951;88:49–92.CrossRefGoogle Scholar
  34. Hancock ML, Miller RR Jr. Nutr Neurosci. 2006;9:121–9.PubMedCrossRefGoogle Scholar
  35. Hayden MR, Tyagi SC. J Nutr. 2004;3:4–36.CrossRefGoogle Scholar
  36. Hazelwood RL. In: Ouellet H, editor. ACTA XIX Congress Intl. Ornithologia, vol. 2. Ottawa: University of Ottawa Press; 1986. p. 2223–33.Google Scholar
  37. Hazelwood RL. In: Whittow GL, editor. Sturkie’s avian physiology. 5th ed. San Diego: Academic; 2000, p. 539–55.CrossRefGoogle Scholar
  38. Hershey T, Perantie DC, Warren SL, Zimmerman EC, Sadler M., White NH. Diabetes Care. 2005;28:2372–7.PubMedCrossRefGoogle Scholar
  39. Hertz L. Neuropharmacology 2008;55:289–309.PubMedCrossRefGoogle Scholar
  40. Jia DY, Liu HJ, Wang FW, Liu SM, Ling EA, Liu K, Hao AJ. Neurosci Lett. 2008;440:27–31.Google Scholar
  41. Kamboj SS, Chopra K, Sandhir R. Metab Brain Dis. 2008;23:427–43.PubMedCrossRefGoogle Scholar
  42. Khandkar M, Jee E, Parmar D, Katare. Biochem J. 1995;307:647–9.PubMedGoogle Scholar
  43. Khare A, Shetty S, Ghosh K, Mohanty D, Chatterjee S. Athersoclerosis 2005;180:375–80.CrossRefGoogle Scholar
  44. Kikuchi G. Mol Cell Biochem. 1973;1:101–14.CrossRefGoogle Scholar
  45. Lanier WL. Can J Anesth. 1999;46:R46–51.PubMedCrossRefGoogle Scholar
  46. Leinninger GM, Vincent AM, Feldman EL. J Peripher Nerv Sys. 2004;9:26–53.CrossRefGoogle Scholar
  47. Leloup C, Magnan C, Alquier T, Mistry S, Offer G, Arnaud E, Kassis N, Ktorza, Penicaud L. Pediatr Res. 2004;56:263–7.PubMedCrossRefGoogle Scholar
  48. Levi A, Eldridge JD, Paterson BM. Science 1985;229:393–5.PubMedCrossRefGoogle Scholar
  49. Levi A, Ferri GL, Watson E, Possenti R, Salton SR. Cell Mol Neurobiol. 2004;24:517–33.PubMedCrossRefGoogle Scholar
  50. Lewin GR, Barde YA. Annu Rev Neurosci. 1996;19:289–317.PubMedCrossRefGoogle Scholar
  51. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS. Trends Neurosci. 1994;17:182–90.PubMedCrossRefGoogle Scholar
  52. Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayuda PV, Arnelle DR, Stamler JS. Proc Natl Acad Sci USA. 1997;94:5923–8.PubMedCrossRefGoogle Scholar
  53. Ma XH, Muzumdar R, Yang XM, Gabriely I, Berger R, Barzilai N. J Gerontol Med Sci. 2002;57A:B225–31.CrossRefGoogle Scholar
  54. Malone JI, Hanna S, Saporta S, Mervis RF, Park CR, Chong L, Giamond DM. Pediatr Diabetes. 2008;9:531–9.PubMedCrossRefGoogle Scholar
  55. Margetic S, Cazzola C, Pegg GG, Hill RA. Int J Obes. 2002;26:1407–1433.Google Scholar
  56. McLeod L, Ray JG. Community Genet. 2002;5:33–9.CrossRefGoogle Scholar
  57. Mooradian AD. Diabetes 1987;36:1094–7.PubMedCrossRefGoogle Scholar
  58. Miller RR Jr. In: Preedy VR, Watson RR, editors. Alcohol in disease: nutrient interactions and dietary intake. Boca Raton: CRC; 2004. p. 339–64.Google Scholar
  59. Miller RR Jr, Leanza CM, Phillips EE, Blacquiere KD. Comp Biochem Physiol. 2003;136B:521–32.Google Scholar
  60. Miller RR Jr, Burum AL, Leithart ME, Hart JD. Comp Biochem Physiol. 2005;141B:323–30.Google Scholar
  61. Miller RR Jr, Hay CM, Striegnitz TR, Honsey LE, Coykendall CE, Blacquiere KD. Comp Biochem Physiol. 2006;144C:23–33.Google Scholar
  62. Miller RR Jr, Coleman K, Yearsley S. 2009; Unpublished data.PubMedCrossRefGoogle Scholar
  63. Min Y, Lowy C, Ghebremeskel K, Thomas B, Offley-Shore B, Crawford M. Am J Clin Nutr. 2005a;82:1162–8.PubMedGoogle Scholar
  64. Min Y, Lowy C, Ghebremeskel K, Thomas B, Crawford M. Diabet Med. 2005b;22:914–20.PubMedCrossRefGoogle Scholar
  65. Musen G, Lyoo KL, Sparks C, Ryan CM, Jimerson DC, Jacobson AM. Diabetes 2006;55:326–33.Google Scholar
  66. Nagai Y, Tasaki H, Takatsu H, Nihei SI, Yamashita K, Nakashima Y. Biochem Biophys Res Commun. 2001;281:726–31.PubMedCrossRefGoogle Scholar
  67. Nahhas F, Barnea E. Am J Reprod Immunol. 1990;22:105–8.PubMedGoogle Scholar
  68. Nakagawa T, Tsuchida A, Itakura Y, Nonmura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Diabetes 2000;49:436–44.PubMedCrossRefGoogle Scholar
  69. Negi G, Kumar A, Sharma SS. Current Res Inf Pharm Sci. 2008;9:62–8.Google Scholar
  70. Norenberg MD, Rama Rao KV. Neurochem Int. 2007;50:983–97.PubMedCrossRefGoogle Scholar
  71. Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA. Diabetes Care. 2001;24:1541–6.PubMedCrossRefGoogle Scholar
  72. Onat A, Hergenc G, Kucukdurmaz Z, Can G, Ayhan E, Bulur S. Clin Nutr. 2008;27:732–9.PubMedCrossRefGoogle Scholar
  73. Ono M, Ichihara J, Nonomura T, Itakura Y, Taiji M, Nakayama C, Noguchi H. Biochem Biophys Res Acta. 1997;238:633–7.Google Scholar
  74. Perantie DC, Wu J, Koller JM, Lim A, Warren SL, Black KJ, Sadler M, White NH, Hershey T. Diabetes Care. 2007;30:2331–7.PubMedCrossRefGoogle Scholar
  75. Perimuter LC, Nathan DM, Goldfinger SH, Russo PA, Yates J, Larkin M. J Diabetes Complicat. 1988;2:210–3.Google Scholar
  76. Ramos-Arroyo MA, Rodriquez-Pinella E, Cordero JF. Eur J Epidemiol. 1992;8:503–8.PubMedCrossRefGoogle Scholar
  77. Reece EA, Pinter E, Leranth CZ, Garcia-Segura M, Sanyal K, Hobbins, JC, Mahoney MJ, Naftolin JC. Teratology 1985;32:363–73.PubMedCrossRefGoogle Scholar
  78. Reitz RC. In: Watson RR, Watzl B, editors. Nutrition and alcohol. Boca Raton: CRC; 1992. p. 191–204.Google Scholar
  79. Rodriquez-Nieto A, Chavarria T, Martinez-Poveda B, Sanchez-Jime, AR, Medina, MA. Biochem Biophys Res Commun. 2002;293:497–500.CrossRefGoogle Scholar
  80. Ryan AS, Nelson EB. Clin Pediatr. 2008;20:1–8.Google Scholar
  81. Salton SR, Ferri GL, Hahm S, Snyder SE, Wilson AJ, Possenti R, Levi A. Front Neuroendocr. 2000;21:199–219.CrossRefGoogle Scholar
  82. Sankarasubbaiyan S, Cooper C, Heilig CW. Am J Kidney Dis. 2001;37:1039–43.PubMedCrossRefGoogle Scholar
  83. Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte DJ. Endocr Rev. 1992;13:387–414.PubMedGoogle Scholar
  84. Scott JF, Robinson GM, French JM, O’Connell JE, Alberti KGMM, Gray CS. Stroke 1999;30:703–99.CrossRefGoogle Scholar
  85. Sendtner M, Holtman B, Hughes RA. Neurochem Res. 1996;21:831–41.PubMedCrossRefGoogle Scholar
  86. Sha H, Xu J, Tang J, Ding J, Gong J, Ge X, Kong D, Gao X. Physiol Genomics. 2007;31:252–63.PubMedCrossRefGoogle Scholar
  87. Sharma JBR, Lee D, Hachinski V, Chan RKT. Neurology 2003;60(Suppl1):A26C.Google Scholar
  88. Selhub J. Annu Rev Nutr. 1999;19:217–46.PubMedCrossRefGoogle Scholar
  89. Skup MH. Acta Neurobiol Exp. 1994;54:81–94.Google Scholar
  90. Song M, Kellum JA, Kaldas H, Fink MP. J Pharmacol Exp Ther. 2004;308:307–16.PubMedCrossRefGoogle Scholar
  91. Srinivasan S, Anitha M, Mwangi S, Heuckeroth RO. Mol Cell Neurosci. 2005;29:118–33.CrossRefGoogle Scholar
  92. Sun W, Oates PJ, Coutcher JB, Gerhardinger C, Lorenzi M. Diabetes 2006;55:2757–62.PubMedCrossRefGoogle Scholar
  93. Tanabe Y, Hashimoto M, Sugioka K, Maruyama M, Fujii Y, Hagiwara R, Hara T, Hossain SM, Shido O. Clin Exp Pharmacol Physiol. 2004;31:700–3.PubMedCrossRefGoogle Scholar
  94. Terwel D, Prickaerts J, Meng F, Jolies J. Eur J Pharmacol. 1995;287:65–71.PubMedCrossRefGoogle Scholar
  95. Tonra JR, Ono M, Liu X, Garcia K, Jackson C, Yancopoulos GD, Wiegand SJ, Wong V. Diabetes 1999;48:588–94.PubMedCrossRefGoogle Scholar
  96. van der Put NMJ, van Straaten HWM, Trijbels FJM, Blom HJ. Exp Biol Med. 2001;226:243–70.Google Scholar
  97. Van Gaal LF, Wauters M, Mertens IL, Considine RV, De Leeuw IH. Int J Obes RelatMetab Disord. 1999;23(Suppl 1):29–36.CrossRefGoogle Scholar
  98. Vincent AM, McLean LL, Backus C, Feldman EL. FASEB J. 2005;19:638–640.Google Scholar
  99. Watson E, Hahm S, Mizuno TM, Windsor J, Montgomery C, Scherer PE, Mobbs CV, Salton SRJ. Endocrinology. 2005;146:5151–5163.Google Scholar
  100. Welsh B, Wecker L. Neurochem Res.1991;16:453–60.PubMedCrossRefGoogle Scholar
  101. Winkler J, Suhr ST, Gage FH, Thal LJ, Fisher LJ. Nature 1995;375:484–7.PubMedCrossRefGoogle Scholar
  102. Wolff SP. Br Med Bull. 1993;49:642–52.PubMedGoogle Scholar
  103. Yamanaka M, Itakura Y, Tsuchida A, Nakagawa T, Taiji M. Biomedical Res. 2008;29:147–53.CrossRefGoogle Scholar
  104. Yuan ZM, Huang Y, Fan MM, Sawyers C, Kharbanda S, Kufee D. J Biol Chem. 1996;271:26457–60.PubMedCrossRefGoogle Scholar
  105. Yuen EC, Howe CL, Li Y, Holtzman, DM, Mobley WC. Brain Dev. 1996;18:362–8.CrossRefGoogle Scholar
  106. Zamboni M, Zoico E, Fantin F, Panagiota Panourgia M, Di Francesco V, Tosoni P, Solerte B, Vettor R, Bosello O. J Gerontol Med Sci. 2004;59A:396–400.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Biology DepartmentHillsdale CollegeHillsdaleUSA

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