L-cysteine supplementation as an adjuvant therapy for type-2 diabetes

Canadian Journal of Physiology and Pharmacology

Volumn 90, Issue 8, 2012, Pages 1061-1064

  Jain, Sushil K ^a  

^a Louisiana State University Health Sciences Center at Shreveport   (United States)

Author keywords

Diabetes; Insulin resistance; L cysteine; Vascular inflammation; Whey protein

Indexed keywords

CYSTEINE;

ADJUVANT THERAPY; DIET SUPPLEMENTATION; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLYCEMIC CONTROL; HUMAN; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; VASCULITIS;

ANIMALS; CYSTEINE; DIABETES MELLITUS, TYPE 2; DIETARY SUPPLEMENTS; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; SIGNAL TRANSDUCTION; UP-REGULATION;

EID: 84864214877     PISSN: 00084212     EISSN: 12057541     Source Type: Journal    
DOI: 10.1139/Y2012-087     Document Type: Review

References (47)

1. L-cysteine complex: evaluations of in vitro insulinomimetic and in vivo blood glucose-lowering activities. Biofactors, 29(4): 213-223. doi:10.1002/biof.5520290405. PMID:18057552.
2. Beard, R.S., Jr, and Bearden, S.E. 2011. Vascular complications of cystathionine b-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research. Am. J. Physiol. Heart Circ. Physiol. 300(1): H13-H26. doi:10.1152/ajpheart.00598.2010. PMID:20971760.
3. Blouet, C., Mariotti, F., Azzout-Marniche, D., Mathé, V., Mikogami, T., Tomé, D., and Huneau, J.F. 2007a. Dietary cysteine alleviates sucrose-induced oxidative stress and insulin resistance. Free Radic. Biol. Med. 42(7): 1089-1097. doi:10.1016/j. freeradbiomed.2007.01.006. PMID:17349935.
4. Blouet, C., Mariotti, F., Mikogami, T., Tome, D., and Huneau, J.F. 2007b. Meal cysteine improves postprandial glucose control in rats fed a high-sucrose meal. J. Nutr. Biochem. 18(8): 519-524. doi:10. 1016/j.jnutbio.2006.10.002. PMID:17142027.
5. Bortolotti, M., Maiolo, E., Corazza, M., Van Dijke, E., Schneiter, P., Boss, A., et al. 2011. Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients. Clin. Nutr. 30 (4): 494-498. doi:10.1016/j.clnu.2011.01.006. PMID:21288612.
6. Cai, W.J., Wang, M.J., Moore, P.K., Jin, H.M., Yao, T., and Zhu, Y.C. 2007. The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation. Cardiovasc. Res. 76(1): 29-40. doi:10.1016/j.cardiores.2007.05.026. PMID:17631873.
7. Chitapanarux, T., Tienboon, P., Pojchamarnwiputh, S., and Leelarungrayub, D. 2009. Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients. J. Gastroenterol. Hepatol. 24(6): 1045-1050. doi:10. 1111/j.1440-1746.2009.05865.x. PMID:19638084.
8. d'Emmanuele di Villa Bianca, R., Sorrentino, R., Maffia, P., Mirone, V., Imbimbo, C., Fusco, F., et al. 2009. Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. Proc. Natl. Acad. Sci. U.S.A. 106(11): 4513-4518. doi:10.1073/pnas.0807974105. PMID:19255435.
9. Darmaun, D., Smith, S.D., Sweeten, S., Hartman, B.K., Welch, C., and Mauras, N. 2008. Poorly controlled type 1 diabetes is associated with altered glutathione homeostasis in adolescents: apparent resistance to N-acetylcysteine supplementation. Pediatr. Diabetes, 9(6): 577-582. doi:10.1111/j.1399-5448.2008.00436.x. PMID:19067892.
10. Diniz, Y.S., Rocha, K.K., Souza, G.A., Galhardi, C.M., Ebaid, G.M., Rodrigues, H.G., et al. 2006. Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats. Eur. J. Pharmacol. 543(1-3): 151-157. doi:10.1016/j.ejphar.2006.05.039. PMID:16814277.
11. Dröge, W. 2005. Oxidative stress and ageing: is ageing a cysteine deficiency syndrome? Philos. Trans. R. Soc. Lond. B Biol. Sci. 360(1464): 2355-2372. doi:10.1098/rstb.2005.1770. PMID: 16321806.
12. Frid, A.H., Nilsson, M., Holst, J.J., and Bjorck, M.E. 2005. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am. J. Clin. Nutr. 82(1): 69-75. PMID:16002802.
13. Haber, C.A., Lam, T.K., Yu, Z., Gupta, N., Goh, T., Bogdanovic, E., et al. 2003. N-acetylcysteine and taurine prevent hyperglycemiainduced insulin resistance in vivo: possible role of oxidative stress. Am. J. Physiol. Endocrinol. Metab. 285(4): E744-E753. PMID: 12799318.
14. Ho, E., Chen, G., and Bray, T.M. 1999. Supplementation of Nacetylcysteine inhibits NFkB activation and protects against alloxan-induced diabetes in CD-1 mice. FASEB J. 13(13): 1845-1854. PMID:10506589.
15. Hsu, C.C., Yen, H.F., Yin, M.C., Tsai, C.M., and Hsieh, C.H. 2004. Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice. J. Nutr. 134(12): 3245-3249. PMID:15570020.
16. Ishigami, M., Hiraki, K., Umemura, K., Ogasawara, Y., Ishii, K., and Kimura, H. 2009. A source of hydrogen sulfide and a mechanism of its release in the brain. Antioxid. Redox Signal. 11(2): 205-214. doi:10.1089/ars.2008.2132. PMID:18754702.
17. Iyer, S.S., Accardi, C.J., Ziegler, T.R., Blanco, R.A., Ritzenthaler, J.D., Rojas, M., et al. 2009. Cysteine redox potential determines proinflammatory IL-1b levels. PLoS ONE, 4(3): e5017. doi:10. 1371/journal.pone.0005017. PMID:19325908.
18. Jain, S.K. 1989. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J. Biol. Chem. 264(35): 21340-21345. PMID:2592379.
19. Jain, S.K., McVie, R., Duett, J., and Herbst, J.J. 1989. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes, 38(12): 1539-1543. doi:10.2337/diabetes.38. 12.1539. PMID:2583378.
20. Jain, S.K., Levine, S.N., Duett, J., and Hollier, B. 1990. Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism, 39(9): 971-975. doi:10.1016/0026-0495(90)90310-9. PMID:2202888.
21. Jain, S.K., Kannan, K., Lim, G., McVie, R., and Bocchini, J.A., Jr. 2002. Hyperketonemia increases TNF-a secretion in cultured U937 monocytes and type-1 diabetic patients and is mediated by oxidative stress and cAMP-deficiency. Diabetes, 51(7): 2287-2293. doi:10.2337/diabetes.51.7.2287. PMID:12086962.
22. Jain, S.K., Kannan, K., Lim, G., Matthews-Greer, J., McVie, R., and Bocchini, J.A., Jr. 2003. Elevated blood interleukin (IL)-6 levels in hyperketonemic type 1 diabetic patients and secretion by acetoacetate-treated cultured U937 monocytes. Diabetes Care, 26 (7): 2139-2143. doi:10.2337/diacare.26.7.2139. PMID:12832326.
23. L-cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, oxidative stress and inhibits NF-kB activation in the livers of Zucker diabetic rats. Free Radic. Biol. Med. 46(12): 1633-1638. doi:10.1016/j.freeradbiomed.2009.03. 014. PMID:19328229.
24. Jain, S.K., Bull, R., Rains, J.L., Bass, P.F., Levine, S.N., Reddy, S., et al. 2010. Low levels of hydrogen sulfide in the blood of diabetic patients and streptozotocin-treated rats causes vascular inflammation? Antioxid. Redox Signal. 12(11): 1333-1337. doi:10.1089/ars.2009.2956. PMID:20092409.
25. Jha, S., Calvert, J.W., Duranski, M.R., Ramachandran, A., and Lefer, D.J. 2008. Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling. Am. J. Physiol. Heart Circ. Physiol. 295(2): H801-H806. doi:10.1152/ajpheart.00377.2008. PMID:18567706.
26. Kabil, O., and Banerjee, R. 2010. Redox biochemistry of hydrogen sulfide. J. Biol. Chem. 285(29): 21903-21907. doi:10.1074/jbc. R110.128363. PMID:20448039.
27. Kaneto, H., Kajimoto, Y., Miyagawa, J., Matsuoka, T., Fujitani, Y., Umayahara, Y., et al. 1999. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes, 48(12): 2398-2406. doi:10.2337/diabetes.48.12.2398. PMID:10580429.
28. Kimura, Y., Goto, Y., and Kimura, H. 2010. Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxid. Redox Signal. 12(1): 1-13. doi:10.1089/ars.2008.2282. PMID:19852698.
29. Li, L., Rose, P., and Moore, P.K. 2011. Hydrogen sulfide and cell signaling. Annu. Rev. Pharmacol. Toxicol. 51(1): 169-187. doi:10. 1146/annurev-pharmtox-010510-100505. PMID:21210746.
30. Lin, C.C., Yin, M.C., Hsu, C.C., and Lin, M.P. 2004. Effect of five cysteine-containing compounds on three lipogenic enzymes in Balb/cA mice consuming a high saturated fat diet. Lipids, 39(9): 843-848. doi:10.1007/s11745-004-1305-4. PMID:15669759.
31. Liu, Z., Li, J., Zeng, Z., Liu, M., and Wang, M. 2008. The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan-and streptozocin-induced diabetic rats. Chem. Biol. Interact. 173(1): 68-75. doi:10.1016/j.cbi.2007.11.012. PMID:18377884.
32. L-cysteine increase PIP3 and glucose utilization by inhibiting PTEN and activating PI3K/AKT/PKCz/l in 3T3L1 adipocytes. J. Biol. Chem. 286(46) 39848-39859. doi:10.1074/jbc.M111.270884. PMID:21953448.
33. Pal, S., Ellis, V., and Dhaliwal, S. 2010. Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br. J. Nutr. 104(5): 716-723. doi:10.1017/S0007114510000991. PMID:20377924.
34. Petersen, B.L., Ward, L.S., Bastian, E.D., Jenkins, A.L., Campbell, J., and Vuksan, V. 2009. A whey protein supplement decreases postprandial glycemia. Nutr. J. 8(1): 47. doi:10.1186/1475-2891-8-47. PMID:19835582.
35. Pieper, G.M., and Siebeneich, W. 1998. Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction. J. Cardiovasc. Pharmacol. 32(1): 101-105. doi:10.1097/00005344-199807000-00016. PMID:9676728.
36. Rains, J., and Jain, S.K. 2011. Oxidative stress, insulin signaling and diabetes. Free Radic. Biol. Med. 50(5): 567-575. doi:10.1016/j. freeradbiomed.2010.12.006. PMID:21163346.
37. Sekhar, R.V., McKay, S.V., Patel, S.G., Guthikonda, A.P., Reddy, V.T., Balasubramanyam, A., and Jahoor, F. 2011a. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care, 34(1): 162-167. doi:10.2337/dc10-1006. PMID:20929994.
38. Sekhar, R.V., Patel, S.G., Guthikonda, A.P., Reid, M., Balasubramanyam, A., Taffet, G.E., and Jahoor, F. 2011b. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am. J. Clin. Nutr. 94(3): 847-853. doi:10.3945/ajcn.110.003483. PMID: 21795440.
39. Shertzer, H.G., Woods, S.E., Krishan, M., Genter, M.B., and Pearson, K.J. 2011. Dietary whey protein lowers the risk for metabolic disease in mice fed a high-fat diet. J. Nutr. 141(4): 582-587. doi:10.3945/jn.110.133736. PMID:21310864.
40. Shibuya, N., Mikami, Y., Kimura, Y., Nagahara, N., and Kimura, H. 2009a. Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J. Biochem. 146(5): 623-626. doi:10.1093/jb/mvp111. PMID:19605461.
41. Shibuya, N., Tanaka, M., Yoshida, M., Ogasawara, Y., Togawa, T., Ishii, K., and Kimura, H. 2009b. 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid. Redox Signal. 11(4): 703-714. doi:10.1089/ars. 2008.2253. PMID:18855522.
42. Song, D., Hutchings, S., and Pang, C.C.Y. 2005. Chronic Nacetylcysteine prevents fructose-induced insulin resistance and hypertension in rats. Eur. J. Pharmacol. 508(1-3): 205-210. doi:10. 1016/j.ejphar.2004.12.018. PMID:15680273.
43. Tanaka, Y., Gleason, C.E., Tran, P.O., Harmon, J.S., and Robertson, R.P. 1999. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc. Natl. Acad. Sci. U. S.A. 96(19): 10857-10862. doi:10.1073/pnas.96.19.10857. PMID:10485916.
44. Wang, Y., Zhao, X., Jin, H., Wei, H., Li, W., Bu, D., et al. 2009. Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoperotein E knockout mice. Arterioscler. Thromb. Vasc. Biol. 29(2): 173-179. doi:10.1161/ATVBAHA.108.179333. PMID:18988885.
45. Whiteman, M., Gooding, K.M., Whatmore, J.L., Ball, C.I., Mawson, D., Skinner, K., et al. 2010. Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulfide. Diabetologia, 53(8): 1722-1726. doi:10.1007/s00125-010-1761-5. PMID:20414636.
46. 2S as a physiologic vasorelaxant: Hypertension in mice with deletion of cystathionine g-lyase. Science, 322(5901): 587-590. doi:10.1126/science.1162667. PMID:18948540.
47. Zavorsky, G.S., Kubow, S., Grey, V., Riverin, V., and Lands, L.C. 2007. An open-label dose-response study of lymphocyte glutathione levels in healthy men and women receiving pressurized whey protein isolate supplements. Int. J. Food Sci. Nutr. 58(6): 429-436. doi:10.1080/09637480701253581. PMID:17710587.