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McCarty MF. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications. Healthcare (Basel). 2017;5(1)doi: 10.3390/healthcare5010015.
McCarty, M. F. (2017). Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications. Healthcare (Basel, Switzerland), 5(1), . https://doi.org/10.3390/healthcare5010015
McCarty, Mark F. "Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications." Healthcare (Basel, Switzerland) vol. 5,1 (2017). doi: https://doi.org/10.3390/healthcare5010015
McCarty MF. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications. Healthcare (Basel). 2017 Mar 14;5(1). doi: 10.3390/healthcare5010015. PMID: 28335416; PMCID: PMC5371921.
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Healthcare (Basel). 2017 Mar 14;5(1). doi: 10.3390/healthcare5010015.

Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications.

Healthcare (Basel, Switzerland)

Mark F McCarty

Affiliations

  1. Catalytic Longevity, 7831 Rush Rose Dr., Apt. 316, Carlsbad, CA 92009, USA. [email protected].

PMID: 28335416 PMCID: PMC5371921 DOI: 10.3390/healthcare5010015

Abstract

Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS), and loss of nitric oxide (NO) bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Phycocyanobilin (PhyCB), the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4). Oxidation of BH4 yields dihydrobiopterin (BH2), which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA), typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to diabetic complications, high dose biotin has the potential to "pinch hit" for diminished NO by direct activation of soluble guanylate cyclase (sGC). High-dose biotin also may aid glycemic control via modulatory effects on enzyme induction in hepatocytes and pancreatic beta cells. Taurine, which suppresses diabetic complications in rodents, has the potential to reverse the inactivating impact of oxidative stress on sGC by boosting synthesis of hydrogen sulfide. Hence, it is proposed that concurrent administration of PhyCB, citrulline, taurine, and supranutritional doses of folate and biotin may have considerable potential for prevention and control of diabetic complications. Such a regimen could also be complemented with antioxidants such as lipoic acid, N-acetylcysteine, and melatonin-that boost cellular expression of antioxidant enzymes and glutathione-as well as astaxanthin, zinc, and glycine. The development of appropriate functional foods might make it feasible for patients to use complex nutraceutical regimens of the sort suggested here.

Keywords: NADPH oxidase; biotin; citrulline; diabetic complications; endothelial nitric oxide synthase; folic acid; nitric oxide; phycocyanobilin; taurine

References

  1. Cardiovasc Ther. 2010 Aug;28(4):e33-45 - PubMed
  2. J Med Food. 2001 Winter;4(4):193-199 - PubMed
  3. Proc West Pharmacol Soc. 1999;42:35-6 - PubMed
  4. Diab Vasc Dis Res. 2010 Oct;7(4):300-10 - PubMed
  5. Diabetes Metab. 2014 Sep;40(4):305-9 - PubMed
  6. J Biol Chem. 2007 Jan 12;282(2):879-87 - PubMed
  7. Neuroscience. 2011 Oct 13;193:399-410 - PubMed
  8. Diabetologia. 2012 Jul;55(7):2069-79 - PubMed
  9. Ophthalmology. 2011 Jul;118(7):1423-8 - PubMed
  10. Mol Biol Rep. 2012 Apr;39(4):3727-35 - PubMed
  11. Glia. 2013 Dec;61(12):1990-9 - PubMed
  12. Tohoku J Exp Med. 2010 Jun;221(2):133-40 - PubMed
  13. J Nutr Biochem. 2013 Jan;24(1):169-77 - PubMed
  14. Nephrol Dial Transplant. 2016 Mar;31(3):391-400 - PubMed
  15. Diabetes Res Clin Pract. 2011 Dec;94(3):e61-4 - PubMed
  16. Diabetologia. 2007 Jul;50(7):1523-31 - PubMed
  17. J Nutrigenet Nutrigenomics. 2011;4(2):90-8 - PubMed
  18. Metabolism. 2014 Mar;63(3):409-14 - PubMed
  19. Diabetes. 2003 Aug;52(8):2144-50 - PubMed
  20. J Am Heart Assoc. 2015 May 28;4(6):e001833 - PubMed
  21. Kidney Int. 2013 Dec;84(6):1189-97 - PubMed
  22. Diabetologia. 2006 May;49(5):1089-96 - PubMed
  23. Am J Physiol Renal Physiol. 2005 Jun;288(6):F1144-52 - PubMed
  24. Biosci Biotechnol Biochem. 2008 May;72(5):1290-8 - PubMed
  25. FEBS Lett. 2003 Dec 18;555(3):601-5 - PubMed
  26. Diabetes Care. 2008 Apr;31(4):747-52 - PubMed
  27. Free Radic Res. 2002 Jun;36(6):695-9 - PubMed
  28. Diabetes Metab. 2015 Sep;41(4):272-81 - PubMed
  29. Biochem Pharmacol. 2014 Apr 1;88(3):275-83 - PubMed
  30. Neural Regen Res. 2012 Nov 25;7(33):2583-91 - PubMed
  31. Diabetes. 2004 Dec;53(12):3233-8 - PubMed
  32. Invest Ophthalmol Vis Sci. 2013 Jan 14;54(1):244-50 - PubMed
  33. J Biol Chem. 1984 May 25;259(10):6393-6 - PubMed
  34. PLoS One. 2016 Jan 14;11(1):e0146438 - PubMed
  35. Biol Trace Elem Res. 2012 Dec;150(1-3):342-9 - PubMed
  36. Med Hypotheses. 1999 May;52(5):401-6 - PubMed
  37. J Immunol. 2004 Sep 15;173(6):3589-93 - PubMed
  38. Methods Enzymol. 2005;396:276-98 - PubMed
  39. Toxicol Mech Methods. 2013 Jan;23(1):27-33 - PubMed
  40. PLoS One. 2014 Aug 12;9(8):e104788 - PubMed
  41. Clin Sci (Lond). 2014 Oct;127(7):499-505 - PubMed
  42. Kidney Int. 2009 Apr;75(8):863 - PubMed
  43. Life Sci. 2006 Jun 13;79(3):225-32 - PubMed
  44. J Assoc Physicians India. 1998 Nov;46(11):939-42 - PubMed
  45. Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1545-52 - PubMed
  46. J Pharmacol Exp Ther. 2005 Aug;314(2):686-92 - PubMed
  47. Clin Chem. 2010 Oct;56(10):1535-43 - PubMed
  48. Diabetes. 2013 Apr;62(4):1258-69 - PubMed
  49. Circ Heart Fail. 2016 Jan;9(1):e002424 - PubMed
  50. J Nutr Sci Vitaminol (Tokyo). 2010;56(1):34-40 - PubMed
  51. Healthcare (Basel). 2016 Jul 08;4(3):null - PubMed
  52. Glia. 2005 Jan 15;49(2):197-210 - PubMed
  53. Biofactors. 2004;20(1):49-59 - PubMed
  54. J Diabetes Complications. 2010 Nov-Dec;24(6):415-23 - PubMed
  55. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):275-90 - PubMed
  56. Biochem Biophys Res Commun. 2003 Oct 24;310(3):979-85 - PubMed
  57. Int J Mol Sci. 2013 Mar 26;14(4):6746-56 - PubMed
  58. Diabetologia. 2013 Apr;56(4):724-36 - PubMed
  59. Diabetes Metab Syndr. 2015 Jan-Mar;9(1):55-64 - PubMed
  60. J Vasc Res. 2014;51(6):439-46 - PubMed
  61. Mol Cell Biol. 2004 Dec;24(24):10941-53 - PubMed
  62. Arch Biochem Biophys. 2004 Mar 1;423(1):126-35 - PubMed
  63. Nephrol Dial Transplant. 2009 Jun;24(6):1884-8 - PubMed
  64. J Diabetes. 2014 May;6(3):221-7 - PubMed
  65. Diab Vasc Dis Res. 2010 Apr;7(2):105-18 - PubMed
  66. Wound Repair Regen. 2003 May-Jun;11(3):198-203 - PubMed
  67. Diabetes. 2003 Mar;52(3):818-23 - PubMed
  68. Nat Med. 2012 Aug;18(8):1279-85 - PubMed
  69. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1068-76 - PubMed
  70. Mult Scler. 2016 Nov;22(13):1719-1731 - PubMed
  71. Kidney Blood Press Res. 2012;36(1):200-8 - PubMed
  72. Planta Med. 2008 Oct;74(13):1526-39 - PubMed
  73. Indian J Endocrinol Metab. 2015 May-Jun;19(3):373-7 - PubMed
  74. J Ethnopharmacol. 1998 Oct;62(3):235-41 - PubMed
  75. Microvasc Res. 2001 Sep;62(2):196-203 - PubMed
  76. Diabetes. 2015 Feb;64(2):631-42 - PubMed
  77. Lancet Diabetes Endocrinol. 2014 Nov;2(11):894-900 - PubMed
  78. Diabetes Metab J. 2015 Oct;39(5):414-23 - PubMed
  79. Diabetologia. 2015 Jan;58(1):113-21 - PubMed
  80. Clin Sci (Lond). 2013 Oct;125(8):361-82 - PubMed
  81. J Biol Chem. 1991 Jun 5;266(16):10035-8 - PubMed
  82. J Biol Chem. 2000 Dec 15;275(50):38957-60 - PubMed
  83. Diab Vasc Dis Res. 2016 Sep;13(5):354-60 - PubMed
  84. Mol Nutr Food Res. 2012 Jun;56(6):900-11 - PubMed
  85. Eur Heart J. 2009 May;30(9):1142-50 - PubMed
  86. J Diabetes Investig. 2014 Mar 23;5(2):228-35 - PubMed
  87. J Am Coll Nutr. 2011 Jun;30(3):210-5 - PubMed
  88. Endothelium. 2004 Mar-Apr;11(2):89-97 - PubMed
  89. Nutr Metab (Lond). 2014 Jan 30;11(1):8 - PubMed
  90. Graefes Arch Clin Exp Ophthalmol. 2015 Feb;253(2):249-59 - PubMed
  91. Free Radic Biol Med. 2010 Sep 15;49(6):1088-98 - PubMed
  92. Indian J Med Res. 2012 Mar;135:422-8 - PubMed
  93. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6754-61 - PubMed
  94. Diabetes. 2005 Nov;54(11):3103-11 - PubMed
  95. J Clin Invest. 2006 Sep;116(9):2552-61 - PubMed
  96. Diabetologia. 1996 Mar;39(3):263-9 - PubMed
  97. Exp Eye Res. 2006 Dec;83(6):1359-65 - PubMed
  98. Circ Res. 2008 Jan 4;102(1):95-102 - PubMed
  99. Metabolism. 2014 Jan;63(1):87-93 - PubMed
  100. Dig Liver Dis. 2012 Sep;44(9):767-74 - PubMed
  101. AACE Clin Case Rep. 2016 Fall;2(4):e370-e373 - PubMed
  102. Diabetes Care. 2006 Nov;29(11):2365-70 - PubMed
  103. Diabetologia. 2016 Feb;59(2):379-89 - PubMed
  104. Mult Scler Relat Disord. 2015 Mar;4(2):159-69 - PubMed
  105. Diabetologia. 2016 Mar;59(3):634-43 - PubMed
  106. Invest Ophthalmol Vis Sci. 2014 Sep 23;55(10):6960-7 - PubMed
  107. Med Hypotheses. 2015 May;84(5):451-5 - PubMed
  108. J Pineal Res. 2016 Jan;60(1):109-17 - PubMed
  109. J Agric Food Chem. 2007 Sep 19;55(19):7962-7 - PubMed
  110. Am J Physiol Endocrinol Metab. 2014 May 15;306(10):E1120-31 - PubMed
  111. Diabetes. 2012 Dec;61(12 ):3270-9 - PubMed
  112. Am J Hypertens. 2005 Feb;18(2 Pt 1):220-6 - PubMed
  113. FASEB J. 2005 Nov;19(13):1890-2 - PubMed
  114. Circulation. 2004 Oct 19;110(16):2484-93 - PubMed
  115. Vasc Med. 2006 May;11(2):101-9 - PubMed
  116. J Atheroscler Thromb. 2014;21(6):519-31 - PubMed
  117. Diabetes Res Clin Pract. 2010 Apr;88(1):103-10 - PubMed
  118. J Clin Endocrinol Metab. 2009 Feb;94(2):410-5 - PubMed
  119. Oman Med J. 2013 May;28(3):195-8 - PubMed
  120. Hypertension. 2007 Oct;50(4):636-42 - PubMed
  121. Free Radic Biol Med. 2001 Dec 1;31(11):1360-7 - PubMed
  122. Biochim Biophys Acta. 2012 Jun;1823(6):1102-9 - PubMed
  123. Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1530-40 - PubMed
  124. J Natl Med Assoc. 2001 Oct;93(10):363-71 - PubMed
  125. J Investig Med. 2011 Dec;59(8):1233-8 - PubMed
  126. J Intercult Ethnopharmacol. 2016 Jan 05;5(1):57-64 - PubMed
  127. Diabetes Care. 2014;37(1):252-8 - PubMed
  128. Ann N Y Acad Sci. 1994 Nov 17;738:257-64 - PubMed
  129. Cancer Res. 2000 Dec 1;60(23):6714-22 - PubMed
  130. Curr Hypertens Rep. 2006 Apr;8(1):54-9 - PubMed
  131. Diabetes. 2014 Aug;63(8):2613-6 - PubMed
  132. J Mol Cell Cardiol. 2009 Dec;47(6):752-60 - PubMed
  133. Lancet. 1993 Aug 28;342(8870):515-8 - PubMed
  134. Biochemistry. 2008 Feb 12;47(6):1819-26 - PubMed
  135. Front Physiol. 2015 Jan 05;5:501 - PubMed
  136. Diabetes Metab. 2016 Dec;42(6):389-397 - PubMed
  137. Biochim Biophys Acta. 2006 Dec;1764(12 ):1890-903 - PubMed
  138. Curr Opin Nephrol Hypertens. 2015 Jan;24(1):74-80 - PubMed
  139. J Nutr. 2004 Oct;134(10 Suppl):2842S-2847S; discussion 2853S - PubMed
  140. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1645-51 - PubMed
  141. Diabetologia. 2002 Jul;45(7):1004-10 - PubMed
  142. Hypertension. 2016 Mar;67(3):541-9 - PubMed
  143. J Complement Integr Med. 2012 Aug 10;9:Article 17 - PubMed
  144. Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):229-40 - PubMed
  145. Arch Toxicol. 2008 Dec;82(12):885-92 - PubMed
  146. Pharmacol Res. 2016 Sep;111:556-62 - PubMed
  147. Acta Diabetol. 1996 Jul;33(2):154-8 - PubMed
  148. Mol Cell Biochem. 2006 Oct;291(1-2):21-8 - PubMed
  149. Int J Mol Sci. 2012;13(6):7521-31 - PubMed
  150. Kidney Int. 2001 Apr;59(4):1342-53 - PubMed
  151. Diabetes Care. 2004 Mar;27(3):765-9 - PubMed
  152. J Med Food. 2007 Dec;10 (4):566-70 - PubMed
  153. Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):15-24 - PubMed
  154. Biofactors. 2007;29(4):203-12 - PubMed
  155. J Biochem Mol Toxicol. 2015 Jun;29(6):274-9 - PubMed
  156. Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R110-20 - PubMed
  157. Pharm Biol. 2016 Aug;54(8):1345-53 - PubMed
  158. J Nutr. 1999 Dec;129(12):2225-30 - PubMed
  159. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3227-45 - PubMed
  160. Circulation. 2013 May 7;127(18):1888-902 - PubMed
  161. J Lipid Res. 2012 Feb;53(2):300-10 - PubMed
  162. Nutrition. 2007 Mar;23(3):261-6 - PubMed
  163. Kidney Int. 2011 Mar;79(6):686; author reply 686-7 - PubMed
  164. Clin Sci (Lond). 2015 Mar;128(5):325-35 - PubMed
  165. Free Radic Biol Med. 2006 Sep 15;41(6):851-61 - PubMed
  166. J Ophthalmol. 2010;2010:746978 - PubMed
  167. J Korean Med Sci. 2012 Oct;27(10):1196-201 - PubMed
  168. Atherosclerosis. 2008 May;198(1):1-11 - PubMed
  169. J Med Food. 2015 Dec;18(12 ):1299-306 - PubMed
  170. Ann N Y Acad Sci. 2000;899:399-402 - PubMed
  171. Food Funct. 2013 Nov;4(11):1586-94 - PubMed
  172. Diabetologia. 2014 Mar;57(3):633-42 - PubMed
  173. Indian J Biochem Biophys. 1997 Dec;34(6):518-23 - PubMed
  174. J Med Food. 2016 Jul;19(7):645-53 - PubMed
  175. Proc West Pharmacol Soc. 1999;42:31-2 - PubMed
  176. J Nutr. 2000 Sep;130(9):2180-7 - PubMed
  177. Med Hypotheses. 2009 Nov;73(5):824-34 - PubMed
  178. N Engl J Med. 1993 Sep 30;329(14):977-86 - PubMed
  179. Adv Nutr. 2016 Jan 15;7(1):14-24 - PubMed
  180. Curr Drug Targets. 2006 Nov;7(11):1505-12 - PubMed
  181. Curr Drug Targets. 2005 Jun;6(4):495-501 - PubMed
  182. J Am Soc Nephrol. 2001 Jan;12(1):124-33 - PubMed
  183. Invest Ophthalmol Vis Sci. 2011 Jul 07;52(8):5093-104 - PubMed
  184. Sci China Life Sci. 2015 Jun;58(6):556-63 - PubMed
  185. Nutr Res. 2013 May;33(5):397-405 - PubMed
  186. Diabetologia. 2014 Feb;57(2):435-46 - PubMed
  187. Circ J. 2014;78(2):300-6 - PubMed
  188. Comp Biochem Physiol C Toxicol Pharmacol. 2003 Apr;134(4):521-7 - PubMed
  189. Eur J Nutr. 2015 Mar;54(2):301-7 - PubMed
  190. J Cell Biochem. 2008 Apr 15;103(6):1925-37 - PubMed
  191. Int J Lab Hematol. 2009 Feb;31(1):1-8 - PubMed
  192. PLoS One. 2014 Oct 09;9(10):e109251 - PubMed
  193. J Nutr Biochem. 2010 Jul;21(7):606-12 - PubMed
  194. Kidney Int. 2010 Nov;78(9):905-19 - PubMed
  195. Arterioscler Thromb Vasc Biol. 2003 Aug 1;23 (8):1455-9 - PubMed
  196. Chin Med J (Engl). 2015 Dec 20;128(24):3276-82 - PubMed
  197. Biochim Biophys Acta. 2015 Nov;1852(11):2474-83 - PubMed
  198. Diabetes. 2011 Apr;60(4):1304-13 - PubMed
  199. Invest Ophthalmol Vis Sci. 2014 Oct 09;55(11):7256-65 - PubMed
  200. Metabolism. 2002 Oct;51(10):1269-73 - PubMed
  201. Front Immunol. 2013 Dec 24;4:480 - PubMed
  202. Med Hypotheses. 2007;69(2):325-32 - PubMed
  203. Exp Eye Res. 1993 Nov;57(5):623-8 - PubMed
  204. Circulation. 2002 Aug 20;106(8):987-92 - PubMed
  205. J Pineal Res. 2013 Mar;54(2):179-89 - PubMed
  206. Br J Surg. 2002 Dec;89(12):1594-601 - PubMed
  207. Med Hypotheses. 2005;64(5):1030-3 - PubMed
  208. Atherosclerosis. 2006 Nov;189(1):236-40 - PubMed
  209. Am J Physiol Cell Physiol. 2007 Nov;293(5):C1679-86 - PubMed
  210. Am J Clin Nutr. 2004 Nov;80(5):1194-200 - PubMed
  211. J Am Soc Nephrol. 2002 Jan;13(1):108-16 - PubMed
  212. Clin Pharmacol. 2014 Nov 28;6:195-204 - PubMed
  213. PLoS One. 2010 Dec 29;5(12 ):e15726 - PubMed
  214. Br J Nutr. 2008 Apr;99(4):756-63 - PubMed
  215. Cardiovasc Diabetol. 2014 Nov 22;13:149 - PubMed
  216. Am Heart J. 2007 Jan;153(1):67-73 - PubMed
  217. Diabetes Res Clin Pract. 2011 May;92 (2):223-7 - PubMed
  218. Free Radic Biol Med. 1999 Apr;26(7-8):944-50 - PubMed
  219. J Am Soc Nephrol. 2012 Nov;23(11):1810-23 - PubMed
  220. J Diabetes Complications. 2015 Nov-Dec;29(8):1223-7 - PubMed
  221. J Pineal Res. 2004 Jan;36(1):1-9 - PubMed
  222. Am J Clin Nutr. 2011 Sep;94(3):847-53 - PubMed
  223. Diabetes. 2007 Mar;56(3):666-74 - PubMed
  224. Mol Cell Biochem. 1994 Mar 30;132(2):127-32 - PubMed
  225. Endocrine. 2015 Nov;50(2):405-12 - PubMed
  226. Ophthalmology. 2012 Jun;119(6):1285-6.e1 - PubMed
  227. Diabetes Care. 2007 Nov;30(11):2899-901 - PubMed
  228. Int J Mol Sci. 2012 Oct 24;13(11):13804-15 - PubMed
  229. Hypertension. 2014 Aug;64(2):323-9 - PubMed
  230. J Nutr Biochem. 2010 Mar;21(3):237-46 - PubMed
  231. Pharm Biol. 2013 May;51(5):539-44 - PubMed
  232. Exp Eye Res. 2009 Dec;89(6):1028-34 - PubMed
  233. Hypertension. 2006 Nov;48(5):950-7 - PubMed
  234. Diabet Med. 2014 Feb;31(2):185-91 - PubMed
  235. J Biol Chem. 2009 Oct 9;284(41):28128-36 - PubMed
  236. J Neurosci. 2010 Sep 8;30(36):11896-901 - PubMed
  237. Clin Chem. 1994 Jan;40(1):18-23 - PubMed
  238. Nihon Rinsho. 1999 Oct;57(10):2261-9 - PubMed
  239. Eye (Lond). 2014 Aug;28(8):1020-7 - PubMed
  240. Int J Cardiol. 2013 Sep 1;167(5):1860-6 - PubMed
  241. J Biol Chem. 2004 Jan 2;279(1):765-71 - PubMed
  242. J Neurochem. 2010 Jan;112(1):77-91 - PubMed
  243. Surgery. 1997 May;121(5):513-9 - PubMed
  244. Amino Acids. 2012 May;42(5):1529-39 - PubMed
  245. Kidney Int. 2008 Oct;74(7):969; author reply 969-70 - PubMed
  246. Clin Endocrinol (Oxf). 2010 Oct;73(4):463-8 - PubMed
  247. JAMA. 2007 Sep 26;298(12):1398-400 - PubMed
  248. J Clin Med Res. 2010 Oct 11;2(5):201-6 - PubMed
  249. J Biol Chem. 2015 May 8;290(19):12014-26 - PubMed
  250. Diabet Med. 2007 Jan;24(1):81-6 - PubMed
  251. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9056-61 - PubMed
  252. Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):166-72 - PubMed
  253. Nat Med. 2003 Nov;9(11):1370-6 - PubMed
  254. Int J Clin Exp Pathol. 2015 May 01;8(5):5097-104 - PubMed
  255. Sci Rep. 2015 Jun 05;5:10987 - PubMed
  256. Life Sci. 2003 Aug 22;73(14):1813-24 - PubMed
  257. Clin Exp Ophthalmol. 2009 Mar;37(2):223-31 - PubMed
  258. Intern Med. 2015;54(2):141-6 - PubMed
  259. Diabetes Metab. 2011 Dec;37(6):505-11 - PubMed
  260. Vascul Pharmacol. 2006 Mar;44(3):143-8 - PubMed
  261. Biol Cell. 2005 Sep;97(9):723-34 - PubMed
  262. J Sex Med. 2011 Mar;8(3):722-33 - PubMed
  263. J Nutr. 2007 Dec;137(12):2680-5 - PubMed
  264. J Clin Invest. 2004 Dec;114(12):1752-61 - PubMed
  265. Diabetes Res Clin Pract. 2011 Oct;94(1):111-8 - PubMed
  266. J Pharmacol Exp Ther. 2016 Mar;356(3):712-9 - PubMed
  267. Saudi J Biol Sci. 2015 Sep;22(5):564-9 - PubMed
  268. Invest Ophthalmol Vis Sci. 2011 Nov 11;52(12 ):8791-8 - PubMed
  269. Diabetes. 2012 Jul;61(7):1838-47 - PubMed
  270. Proc Soc Exp Biol Med. 1996 Apr;211(4):323-31 - PubMed
  271. Diabetologia. 2012 Sep;55(9):2522-32 - PubMed
  272. Mol Cell Biochem. 1988 Jan;79(1):47-55 - PubMed
  273. Med Hypotheses. 2010 Mar;74(3):596-600 - PubMed
  274. Br J Pharmacol. 2015 Oct;172(19):4684-98 - PubMed
  275. Arzneimittelforschung. 2011;61(4):239-46 - PubMed
  276. Eur J Pharmacol. 2015 Jan 5;746:106-14 - PubMed
  277. Diabetes. 2016 Oct;65(10):3171-84 - PubMed
  278. J Endocrinol Invest. 2012 Oct;35(9):824-7 - PubMed
  279. Diabetes. 2006 Jan;55(1):102-9 - PubMed
  280. J Trace Elem Med Biol. 2013 Apr;27(2):137-42 - PubMed
  281. Nutr Res Pract. 2008 Winter;2(4):295-300 - PubMed
  282. Nutrition. 2015 Sep;31(9):1148-54 - PubMed
  283. Diabetes Metab. 2015 Nov;41(5):429-31 - PubMed
  284. Diabetes Care. 2009 Nov;32(11):2084-6 - PubMed
  285. Atherosclerosis. 2010 May;210(1):226-31 - PubMed
  286. Diabet Med. 2014 Nov;31(11):1316-22 - PubMed
  287. Diabetologia. 2011 Aug;54(8):2183-91 - PubMed
  288. PLoS One. 2013 May 22;8(5):e64148 - PubMed
  289. Bangladesh Med Res Counc Bull. 2005 Aug;31(2):62-7 - PubMed
  290. Arch Biochem Biophys. 1968 Sep 20;127(1):17-21 - PubMed
  291. Circulation. 2012 May 15;125(19):2323-33 - PubMed
  292. Br J Nutr. 2009 Jan;101(2):270-7 - PubMed
  293. Diabetes. 2014 Aug;63(8):2845-53 - PubMed
  294. Biol Trace Elem Res. 2014 May;158(2):211-8 - PubMed
  295. PeerJ. 2016 May 12;4:e2022 - PubMed
  296. Science. 1982 Jun 18;216(4552):1329-30 - PubMed
  297. Physiol Behav. 2015 Nov 1;151:412-20 - PubMed
  298. J Am Soc Nephrol. 2012 Nov;23 (11):1835-46 - PubMed
  299. Pharmacol Rep. 2015 Feb;67(1):17-23 - PubMed
  300. Diabetes. 1996 Oct;45(10):1329-35 - PubMed
  301. Diabetes Care. 1995 Aug;18(8):1160-7 - PubMed
  302. Invest Ophthalmol Vis Sci. 2012 Jul 24;53(8):4881-8 - PubMed
  303. Future Med Chem. 2013 Jun;5(10):1075-8 - PubMed
  304. FEBS J. 2010 Dec;277(24):5061-71 - PubMed
  305. Circulation. 2012 Nov 27;126(22):2556-64 - PubMed
  306. Cardiovasc Diabetol. 2015 Oct 31;14:145 - PubMed
  307. PLoS One. 2014 Feb 18;9(2):e88899 - PubMed
  308. Biomed Pharmacother. 1990;44(10):511-4 - PubMed
  309. Arch Med Res. 2012 Aug;43(6):476-81 - PubMed
  310. Curr Pharm Des. 2008;14 (25):2613-8 - PubMed
  311. Biochem Biophys Res Commun. 2015 Mar 20;458(4):869-76 - PubMed
  312. Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1053-61 - PubMed
  313. J Pineal Res. 2011 Mar;50(2):124-31 - PubMed
  314. Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E481-95 - PubMed
  315. Front Immunol. 2013 Sep 26;4:293 - PubMed
  316. J Diabetes Complications. 2015 Mar;29(2):218-21 - PubMed
  317. J Mol Med (Berl). 2014 May;92(5):441-52 - PubMed
  318. Curr Med Chem. 2013;20(26):3226-33 - PubMed
  319. Med Hypotheses. 2006;66(2):323-8 - PubMed
  320. Diabetes. 2015 Apr;64(4):1459-69 - PubMed
  321. Pharmacology. 2004 Nov;72(3):190-5 - PubMed
  322. Front Endocrinol (Lausanne). 2013 Apr 03;4:40 - PubMed
  323. Br J Pharmacol. 2013 Jun;169(3):619-31 - PubMed
  324. World J Diabetes. 2013 Aug 15;4(4):124-9 - PubMed
  325. Life Sci. 2004 May 28;75(2):215-24 - PubMed
  326. Circulation. 2006 Sep 12;114(11):1193-201 - PubMed
  327. Mar Drugs. 2013 Mar 21;11(3):960-74 - PubMed
  328. Br J Clin Pharmacol. 2008 Jan;65(1):51-9 - PubMed
  329. Free Radic Biol Med. 2014 Oct;75:129-39 - PubMed
  330. Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1174-81 - PubMed
  331. J Diabetes. 2011 Sep;3(3):217-24 - PubMed
  332. Am J Cardiol. 2008 May 22;101(10A):58D-68D - PubMed
  333. J Diabetes Metab Disord. 2015 Jul 28;14:63 - PubMed
  334. J Neurol Sci. 2013 Jan 15;324(1-2):40-4 - PubMed
  335. Nephron. 1999;83(4):361-2 - PubMed
  336. J Nutr Sci Vitaminol (Tokyo). 1997 Jun;43(3):271-80 - PubMed
  337. Nephrol Dial Transplant. 2013 Jul;28(7):1751-61 - PubMed
  338. Diabetes Care. 2014;37(1):17-23 - PubMed
  339. Neuropharmacology. 2010 Mar;58(3):585-92 - PubMed
  340. Mol Vis. 2012;18:439-48 - PubMed
  341. Atheroscler Suppl. 2003 Dec;4(4):41-51 - PubMed
  342. Diab Vasc Dis Res. 2013 Sep;10 (5):436-41 - PubMed
  343. J Pineal Res. 2003 Oct;35(3):212-20 - PubMed

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