• 1
    Kahn, B.B. (1998) Type 2 diabetes: when insulin secretion fails to compensate for insulin resistance. Cell 92, 593596.
  • 2
    Stumvoll, M. (1998) Pathogenesis of type II diabetes mellitus. Futura 13, 174181.
  • 3
    Boden, G. (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46, 310.
  • 4
    Rebrin, K., Steil, G.M., Getty, L. & Bergman, R.N. (1994) Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes 44, 10381045.
  • 5
    Shimabukuro, M., Zhou, Y.-T., Levi, M. & Unger, R.H. (1998) Fatty acid induced β cell apoptosis: a link between obesity and diabetes. Proc. Natl Acad. Sci. USA 95, 24982502.
  • 6
    Randle, P.J., Priestman, D.A., Mistry, S.C. & Halsall, A.J. (1994) Glucose fatty acid interactions and the regulation of glucose disposal. J. Cell. Biochem. 55, 111.
  • 7
    Gura, T. (1997) Obesity sheds its secrets. Science 275, 751753.
  • 8
    Patti, M.E. & Kahn, C.R. (1996) Lessons from transgenic and knockout animals about non-insulin-dependent diabetes mellitus. Trends Endocrinol. Metabol. 7, 311319.
  • 9
    Hotamisligil, G.S., Shepherd, P.R., Whiters, D.J. & Siddle, K. (1998) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Biochem. J. 333, 471490.
  • 10
    Hotamisligil, G.S., Arner, P., Caro, J.F., Atkinson, R.L. & Spiegelmann, B.M. (1995) Increased adipose tissue expression of tumor necrosis factor alpha in human obesity and insulin resistance. J. Clin. Invest. 95, 24092415.
  • 11
    Saghizadeh, M., Ong, J.M., Garvey, T.W., Henry, R. & Kern, P.A. (1996). The expression of TNF alpha by human muscle. J. Clin. Invest. 97, 11111116.
  • 12
    Kern, P.A. (1997) Obesity: common symptom of diverse gene based metabolic dysregulations. Potential role of TNF and lipoprotein lipase as candidate genes for obesity. J. Nutr.127, 1917–22.
  • 13
    Lang, C.H., Dobrescu, C. & Bagby, G.J. (1992) Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 130, 4352.
  • 14
    Zhang, S. & Kim, K.H. (1995) TNF alpha inhibits glucose induced insulin secretion in a pancreatic beta cell line (INS-1). FEBS Lett. 377, 237239.
  • 15
    Uysal, K.T., Wiesbrock, S.M., Marino, M.A. & Hotamisligil, G.S. (1997). Protection from obesity-induced insulin resistance in mice lacking TNF function. Nature (London) 389, 610614.
  • 16
    Schreyer, S.A., Streamson, C.C. Jr & LeBoef, R.C. (1998) Obesity and diabetes in TNF-alpha receptor deficient mice. J. Clin. Invest. 102, 402411.
  • 17
    Shepherd, P.R., Whiters, D.J. & Siddle, K. (1998) Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem. J. 333, 471490.
  • 18
    White, M.F. & Kahn, C.R. (1994) The insulin signaling system. J. Biol. Chem. 269, 14.
  • 19
    Alessi, D.R. & Cohen, P. (1998) Mechanism of activation and function of protein kinase B. Curr. Opin. Genet. Dev. 8, 5562.
  • 20
    Ueki, K., Yamamoto-Honda, R., Kaburagi, Y., Yamauchi, T., Tobe, K., Burgering, B.M., Coffer, P.J., Komuro, I., Akanuma, Y., Yazaki, Y. & Kadowaki, T. (1998) Potential role of PKB in insulin-induced glucose transport, glycogen synthesis and protein synthesis. J. Biol. Chem. 273, 53155322.
  • 21
    Begum, N., Ragolia, L. & Srinivasan, M. (1996) Effect of tumor necrosis factor alpha on insulin stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. Eur. J. Biochem. 238, 214220.
  • 22
    Irintchev, A., Langer, M., Zweyer, M., Theisen, R. & Wernig, A. (1997) Functional improvement of damaged adult mouse muscle by implantation of primary myoblasts. J. Physiol. (London) 500, 775758.
  • 23
    Storz, P., Döppler, H., Wernig, A., Pfizenmaier, K. & Müller, G. (1998) TNF inhibits insulin induced STAT5 activation in differentiated mouse muscle cells pmi28. FEBS Lett. 440, 4145.
  • 24
    Bourteele, S., Hauβer, A., Döppler, H., Horn-Müller, J., Röpke, C., Schwarzmann, G., Pfizenmaier, K. & Müller, G. (1998) Tumor Necrosis Factor induces ceramide oscillations and negatively controls sphingolipid synthases by caspases in apoptotic Kym-1 cells. J. Biol. Chem. 273, 3124531251.
  • 25
    Gold, M.R., Duronio, V., Saxena, S.P., Schrader, J.W. & Aebersold, R. (1994) Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoetic cells. Association of the enzyme with various tyrosine-phosphorylated proteins. J. Biol. Chem. 269, 54035412.
  • 26
    Skolnik, E.Y. & Marcusohn, J. (1996) Inhibition of insulin receptor signaling by TNF: potential role in obesity and non-insulin-dependent diabetes mellitus. Cytokine Growth Factor Rev. 7, 161173.
  • 27
    Mückler, M. (1994) Facilitative glucose transporters. Eur. J. Biochem. 219, 713725.
  • 28
    Peterson, K.F., Hendler, R., Price, T., Perseghin, G., Rothman, D.L., Held, N., Amatruda, J.M. & Shulman, G.I. (1998) 13C/31P NMR studies on the mechanism of insulin resistance in obesity. Diabetes 47, 381386.
  • 29
    Maggs, D.G., Jakcob, R., Rife, F., Lange, R., Leone, P., During, M.J., Tamborlane, W.V. & Sherwin, R.S. (1995) Interstitial fluid concentrations of gylcerol, glucose, and amino acids in human quadriceps muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle. J. Clin. Invest. 96, 370377.
  • 30
    Goodyear, L.J., Giorgino, F., Sherman, L.A., Carey, J., Smith, R.J. & Dohm, G.L. (1995) Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J. Clin. Invest. 95, 21952204.
  • 31
    Garvey, W.T., Maianu, L., Hancock, J.A., Golichowski, A.M. & Baron, A. (1992) Gene expression of GLUT4 in skeletal muscle of patients with obesity IGT, GDM and NIDDM. Diabetes 41, 465475.
  • 32
    Brüning, J.C., Winnay, J., Bonner-Weir, S., Taylor, S.I., Accli, D. & Kahn, R.C. (1997) Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88, 561572.
  • 33
    Stephens, J.M., Lee, J. & Pilch, P.F. (1997) Tumor necrosis factor induced insulin resistance in 3T3 L1 adipocytes is accompanied by a loss of insulin receptor substrate and GLUT4 expression without a loss of insulin receptor mediated signal transduction. J. Biol. Chem. 272, 971976.
  • 34
    Okada, T., Kawano, T., Sakakibara, T., Hazeki, O. & Ui, M. (1994) Essential role of phosphatidylinositol 3-kinase in insulin induced glucose transport and antilipolysis in rat adipocytes. J. Biol. Chem. 269, 35683573.
  • 35
    Whiters, D.J., Gutierrez, J.S., Towery, H., Burks, D.J., Ren, J.-M., Previs, S., Zhang, Y., Bernal, D., Pons, S., Shulman, G.I., Bonner-Weir, S. & White, M.F. (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature (London) 391, 900903.
  • 36
    Rondinone, C.M., Wang, L.-M., Lonnroth, P., Wesslau, C., Pierce, J.H. & Smith, U. (1997) Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidyl 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus. Proc. Natl Acad. Sci. USA 94, 41714175.
  • 37
    Ranganathan, S. & Davidson, M.B. (1996) Effect of tumor necrosis factor on basal and insulin stimulated glucose transport in cultured muscle and fat cells. Metabolism 45, 10891094.
  • 38
    Nolte, L.A., Hansen, P.A., Chen, M.M., Schluter, J.M., Gulve, E.A. & Holloszy, J.O. (1998) Short term exposure to tumor necrosis factor does not affect insulin stimulated glucose uptake in skeletal muscle. Diabetes 47, 721726.
  • 39
    Ciaraldi, T.P., Carter, L., Mudaliar, S., Kern, P.A. & Henry, R.R. (1998) Effects of tumor necrosis factor alpha on glucose metabolism in cultured human muscle cells from nondiabetic and type 2 diabetic subjects. Endocrinology 139, 47934800.
  • 40
    McGowan, K.M., Police, S., Winslow, J.B. & Pekala, P.H. (1997). Tumor necrosis factor alpha regulation of glucose transporter (GLUT1) mRNA turnover. Contribution of the 3′-untranslated region of the GLUT1 message. J. Biol. Chem. 272, 13311337.
  • 41
    Sakurai, Y., Zhang, X.J. & Wolfe, R.R. (1996) TNF directly stimulates glucose uptake and leucine oxidation and inhibits nonesterified fatty acid flux. Am. J. Physiol. 270, E864E872.
  • 42
    Furnsinn, C., Neschen, S., Wagner, O., Roden, M., Bisschop, M. & Waldhausl, W. (1997) Acute and chronic exposure to tumor necrosis factor-alpha fails to affect insulin-stimulated glucose metabolism of isolated rat soleus muscle. Endocrinology 138, 26742679.
  • 43
    Brozinick, J.T. Jr & Birnbaum, M.J. (1998) Insulin but not contraction activates Akt/PKB in isolated rat skeletal muscle. J. Biol. Chem. 173, 1467914682.
  • 44
    Krook, A., Roth, R.A., Jiang, X.J., Zierath, J.R. & Wallberg-Henrikson, H. (1998) Insulin stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects. Diabetes 47, 12811286.
  • 45
    Brüning, J.C., Michael, M.D., Winnay, J.N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L.J. & Kahn, C.R. (1998) A muscle specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell. 2, 559569.
  • 46
    Katz, E.B., Stenbit, A.E., Hatton, K., DePinho, R. & Charron, M.J. (1997) Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature (London) 377, 151155.
  • 47
    Stenbit, A.E., Tsao, T.-S., Li, J., Burcelin, R., Geenen, D.L., Factor, S.M., Houseknecht, K., Katz, E.B. & Charron, M.J. (1997) GLUT4 heterzygous knockout mice develop muscle insulin resistance and diabetes. Nat. Med. 3, 10961101.
  • 48
    Moitra, J., Mason, M.M., Olive, M., Krylov, D., Gavrilova, O., Marcus-Samuels, B., Feigenbaum, L., Lee, E., Aoyama, T., Eckhaus, M., Reitman, M.L. & Vinson, C. (1998) Life without white fat: a transgenic mouse. Genes Dev. 12, 31683181.
  • 49
    Peraldi, P. & Spiegelman, B. (1998) TNF-alpha and insulin resistance: summary and future prospects. Mol. Cell. Biochem. 182, 169175.