Ras inhibition induces insulin sensitivity and glucose uptake

PLoS ONE

Volumn 6, Issue 6, 2011, Pages

  Mor, Adi ^a   Aizman, Elizabeta ^a   George, Jacob ^b,c   Kloog, Yoel ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b KAPLAN MEDICAL CENTER   (Israel)

^c HEBREW UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

5 FLUORO FARNESYLTHIOSALICYLIC ACID; GLUCOSE TRANSPORTER 4; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; RAS PROTEIN; THIOSALICYLIC ACID; UNCLASSIFIED DRUG; DRUG DERIVATIVE; FARNESOL; GLUCOSE; PROTEIN P21; SALICYLIC ACID DERIVATIVE; SALIRASIB;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; GLUCOSE TRANSPORT; HYPERGLYCEMIA; IMMUNOBLOTTING; IN VITRO STUDY; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS INHIBITION; SIGNAL TRANSDUCTION; ANIMAL; CELL LINE; DRUG ANTAGONISM; METABOLISM; PHYSIOLOGY; POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

MUS;

ANIMALS; BLOTTING, WESTERN; CELL LINE; DIABETES MELLITUS, TYPE 2; FARNESOL; GLUCOSE; INSULIN RESISTANCE; MICE; POLYMERASE CHAIN REACTION; PROTO-ONCOGENE PROTEINS P21(RAS); SALICYLIC ACIDS;

EID: 79959677545     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0021712     Document Type: Article

References (46)

1. Reaven GM, (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595-1607.
2. Defronzo RA, (2009) Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58: 773-795.
3. Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF, (2007) Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148: 241-251.
4. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM, (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Journal of Clinical Investigations 95: 2409-2415.
5. Weigert C, Hennige AM, Lehmann R, Brodbeck K, Baumgartner F, et al. (2006) Direct cross-talk of interleukin-6 and insulin signal transduction via insulin receptor substrate-1 in skeletal muscle cells. Journal of Biological Chemistry 281: 7060-7067.
6. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS, (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389: 610-614.
7. Franckhauser S, Elias I, Rotter Sopasakis V, Ferre T, Nagaev I, et al. (2008) Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice. Diabetologia 51: 1306-1316.
8. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, et al. (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11: 191-198.
9. Das UN, (2002) Obesity, metabolic syndrome X, and inflammation. Nutrition 18: 430-432.
10. Itani SI, Ruderman NB, Schmieder F, Boden G, (2002) Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51: 2005-2011.
11. Sinha S, Perdomo G, Brown NF, O'Doherty RM, (2004) Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor kappa B. Journal of Biological Chemistry 279: 41294-41301.
12. Jove M, Planavila A, Sanchez RM, Merlos M, Laguna JC, et al. (2006) Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology 147: 552-561.
13. Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, et al. (2007) A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. Journal of Biological Chemistry 282: 35279-35292.
14. Bar Sagi D, Hall A, (2000) Ras and Rho GTPases: a family reunion. Cell 103 (2): 227-238.
15. Boguski MS, McCormick F, (1993) Proteins regulating Ras and its relatives. Nature 366: 643-654.
16. Bar-Sagi D, Hall A, (2000) Ras and Rho GTPases: a family reunion. Cell 103: 227-238.
17. Bos JL, (1989) ras oncogenes in human cancer: a review. Cancer Res 49: 4682-4689.
18. Downward J, (1998) Ras signalling and apoptosis. Curr Opin Genet Dev 8: 49-54.
19. McFall A, Ulku A, Lambert QT, Kusa A, Rogers-Graham K, et al. (2001) Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase. Mol Cell Biol 21: 5488-5499.
20. Cox AD, Der CJ, (2002) Ras family signaling: therapeutic targeting. Cancer Biol Ther 1: 599-606.
21. Philips MR, (2005) Compartmentalized signalling of Ras. Biochem Soc Trans 33: 657-661.
22. Rotblat B, Ehrlich M, Haklai R, Kloog Y, (2008) The Ras inhibitor farnesylthiosalicylic acid (Salirasib) disrupts the spatiotemporal localization of active Ras: a potential treatment for cancer. Methods Enzymol 439: 467-489.
23. George J, Afek A, Keren P, et al. (2002) Functional inhibition of Ras by S-trans,trans-farnesyl thiosalicylic acid attenuates atherosclerosis in apolipoprotein E knockout mice. Circulation 105: 2416-2422.
24. Karusis D, Abramsky O, Grigoriadis N, Chapman J, Mizrachi-Koll R, et al. (2001) The Ras-pathway inhibitor S,trans-trans farnesythiosalicylic acid (FTS) suppresses experimental allergic encephalomyelitis. J Neuroimmunol in press.
25. Katsav A, Kloog Y, Korczyn AD, et al. (2001) Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS). Clin Exp Immunol 126: 570-577.
26. Katzav A, Kloog Y, Korczyn AD, Molina V, Blank M, et al. (2003) Inhibition of ras by farnesylthiosalicylate significantly reduces the levels of autoantibodies in two animal models of the antiphospholipid syndrome. Immunobiology 207: 47-50.
27. Kane LP, Shapiro VS, Stokoe D, Weiss A, (1999) Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol 9: 601-604.
28. Aharonson Z, Gana-Weisz M, Varsano T, Haklai R, Marciano D, et al. (1998) Stringent structural requirements for anti-Ras activity of S-prenyl analogues. Biochim Biophys Acta 1406: 40-50.
29. Aizman E, Mor A, George J, Kloog Y, (2010) Ras inhibition attenuates pancreatic cell death and experimental type 1 diabetes: possible role of regulatory T cells. European Journal of Pharmacology 643: 139-144.
30. Mor A, Keren G, Kloog Y, George J, (2008) N-Ras or K-Ras inhibition increases the number and enhances the function of Foxp3 regulatory T cells. European Journal of Immunology 38: 1493-1502.
31. Mor A, Kloog Y, Keren G, George J, (2009) Ras inhibition increases the frequency and function of regulatory T cells and attenuates type-1 diabetes in non-obese diabetic mice. European Journal of Pharmacology 616: 301-305.
32. Frost JA, Swantek JL, Stippec S, Yin MJ, Gaynor R, et al. (2000) Stimulation of NFkappa B activity by multiple signaling pathways requires PAK1. Journal of Biological Chemistry 275: 19693-19699.
33. Louzao MC, Espina B, Vieytes MR, Vega FV, Rubiolo JA, et al. (2008) "Fluorescent glycogen" formation with sensibility for in vivo and in vitro detection. Glycoconj J 25: 503-510.
34. Wang L, Liu Y, Yan Lu S, Nguyen KT, Schroer SA, et al. (2010) Deletion of Pten in Pancreatic {beta}-Cells Protects Against Deficient {beta}-Cell Mass and Function in Mouse Models of Type 2 Diabetes. Diabetes 59: 3117-3126.
35. Jove M, Planavila A, Laguna JC, Vazquez-Carrera M, (2005) Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells. Endocrinology 146: 3087-3095.
36. Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, et al. (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 44: 645-651.
37. Genot E, Cleverley S, Henning S, Cantrell D, (1996) Multiple p21ras effector pathways regulate nuclear factor of activated T cells. EMBO J 15: 3923-3933.
38. Genot E, Cantrell DA, (2000) Ras regulation and function in lymphocytes. Curr Opin Immunol 12: 289-294.
39. Karussis D, Abramsky O, Grigoriadis N, Chapman J, Mizrachi-Koll R, et al. (2001) The Ras-pathway inhibitor, S-trans-trans-farnesylthiosalicylic acid, suppresses experimental allergic encephalomyelitis. J Neuroimmunol 120: 1-9.
40. Kloog Y, Cox AD, (2000) RAS inhibitors: potential for cancer therapeutics. Mol Med Today 6: 398-402.
41. DeFronzo RA, Ferrannini E, (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173-194.
42. Taniguchi CM, Emanuelli B, Kahn CR, (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7: 85-96.
43. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, et al. (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11: 183-190.
44. Karin M, Takahashi T, Kapahi P, Delhase M, Chen Y, et al. (2001) Oxidative stress and gene expression: the AP-1 and NF-kappaB connections. Biofactors 15: 87-89.
45. Bjornholm M, Zierath JR, (2005) Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes. Biochemical Society Transactions 33: 354-357.
46. Shalom-Feuerstein R, Levy R, Makovski V, et al. (2008) Galectin-3 regulates RasGRP4-mediated activation of N-Ras and H-Ras. Biochim Biophys Acta 1783: 985-993.