Skip to main content
SpringerLink
Log in

Insulin Resistance in the Metabolic Syndrome

  • Chapter
  • First Online:
Metabolic Basis of Obesity

Abstract

In 1988, Gerald Reaven coined the term “Syndrome X” to describe a complex of metabolic abnormalities, including glucose intolerance, hypertriglyceridemia and reduced levels of HDL-cholesterol, present in individuals at increased risk for cardiovascular disease [1]. Since then, attempts to quantify cardiovascular disease risk have led to the development of clinical criteria for the diagnosis of this syndrome, now known as the “metabolic syndrome” or “insulin resistance syndrome”. Although these criteria continue to evolve, those put forth by the National Cholesterol Education Program (NCEP), World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), International Diabetes Federation (IDF) and American Association of Clinical Endocrinologists (AACE), all include hyperglycemia, hypertriglyceridemia, low HDL-cholesterol and hypertension (reviewed in [2)] (Table 1). It is clear now that the metabolic syndrome is associated with many diseases in addition to cardiovascular disease. These include cholesterol gallstones, non-alcoholic fatty liver disease, which ranges from benign steatosis to non-alcholic steatohepatitis (NASH), polycystic ovary disease (PCOS) and neurodegenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Reaven, G. M. (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes, 37(12), 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  2. Cornier, M. A., Dabelea, D., Hernandez, T. L., et al. (2008). The metabolic syndrome. Endocrine Reviews, 29(7), 777–822.

    Article  PubMed  CAS  Google Scholar 

  3. Ford, E. S., Giles, W. H., & Mokdad, A. H. (2004). Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care, 27(10), 2444–2449.

    Article  PubMed  Google Scholar 

  4. Kahn, R., Buse, J., Ferrannini, E., & Stern, M. (2005). The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 28(9), 2289–2304.

    Article  PubMed  Google Scholar 

  5. Reaven, G. (2004). The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinology and Metabolism Clinics of North America, 33(2), 283–303.

    Article  PubMed  Google Scholar 

  6. Yamaguchi, Y., Flier, J. S., Benecke, H., Ransil, B. J., & Moller, D. E. (1993). Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology, 132(3), 1132–1138.

    Article  PubMed  CAS  Google Scholar 

  7. Leibiger, B., Leibiger, I. B., Moede, T., et al. (2001). Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. Molecular cell, 7(3), 559–570.

    Article  PubMed  CAS  Google Scholar 

  8. Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006). Critical nodes in signalling pathways: insights into insulin action. Nature Reviews. Molecular Cell Biology, 7(2), 85–96.

    Article  PubMed  CAS  Google Scholar 

  9. Fasshauer, M., Klein, J., Ueki, K., et al. (2000). Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes. The Journal of Biological Chemistry, 275(33), 25494–25501.

    Article  PubMed  CAS  Google Scholar 

  10. Wu, J., Tseng, Y. D., Xu, C. F., Neubert, T. A., White, M. F., & Hubbard, S. R. (2008). Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nature Structural & Molecular Biology, 15(3), 251–258.

    Article  CAS  Google Scholar 

  11. Hirashima, Y., Tsuruzoe, K., Kodama, S., et al. (2003). Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway. The Journal of Endocrinology, 179(2), 253–266.

    Article  PubMed  CAS  Google Scholar 

  12. Kubota, N., Kubota, T., Itoh, S., et al. (2008). Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell Metabolism, 8(1), 49–64.

    Article  PubMed  CAS  Google Scholar 

  13. Oriente, F., Andreozzi, F., Romano, C., et al. (2005). Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3 epsilon. The Journal of Biological Chemistry, 280(49), 40642–40649.

    Article  PubMed  CAS  Google Scholar 

  14. Luan, B., Zhao, J., Wu, H., et al. (2009). Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance. Nature, 457(7233), 1146–1149.

    Article  PubMed  CAS  Google Scholar 

  15. Bard-Chapeau, E. A., Hevener, A. L., Long, S., Zhang, E. E., Olefsky, J. M., & Feng, G. S. (2005). Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action. Nature Medicine, 11(5), 567–571.

    Article  PubMed  CAS  Google Scholar 

  16. Biddinger, S. B., & Kahn, C. R. (2006). From mice to men: insights into the insulin resistance syndromes. Annual Review of Physiology, 68, 123–158.

    Article  PubMed  CAS  Google Scholar 

  17. Brachmann, S. M., Ueki, K., Engelman, J. A., Kahn, R. C., & Cantley, L. C. (2005). Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice. Molecular and Cellular Biology, 25(5), 1596–1607.

    Article  PubMed  CAS  Google Scholar 

  18. Terauchi, Y., Tsuji, Y., Satoh, S., et al. (1999). Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nature Genetics, 21(2), 230–235.

    Article  PubMed  CAS  Google Scholar 

  19. Cheatham, B., Vlahos, C. J., Cheatham, L., Wang, L., Blenis, J., & Kahn, C. R. (1994). Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Molecular and Cellular Biology, 14(7), 4902–4911.

    PubMed  CAS  Google Scholar 

  20. Shepherd, P. R., Withers, D. J., & Siddle, K. (1998). Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. The Biochemical Journal, 333, (Pt 3):471–490.

    PubMed  CAS  Google Scholar 

  21. Bishop, A. L., & Hall, A. (2000). Rho gtpases and their effector proteins. The Biochemical Journal, 348, Pt 2:241–255.

    Article  PubMed  CAS  Google Scholar 

  22. Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860–867.

    Article  PubMed  CAS  Google Scholar 

  23. Vanhaesebroeck, B., & Alessi, D. R. (2000). The PI3K-PDK1 connection: more than just a road to PKB. The Biochemical Journal, 346, Pt 3:561–576.

    Article  PubMed  CAS  Google Scholar 

  24. Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005). Phosphorylation and regulation of Akt/PKB by the rictor-mtor complex. Science, 307(5712), 1098–1101.

    Article  PubMed  CAS  Google Scholar 

  25. Bandyopadhyay, G., Standaert, M. L., Zhao, L., et al. (1997). Activation of protein kinase C (alpha, beta, and zeta) by insulin in 3T3/L1 cells. Transfection studies suggest a role for PKC-zeta in glucose transport. The Journal of Biological Chemistry, 272(4), 2551–2558.

    Article  PubMed  CAS  Google Scholar 

  26. Tremblay, F., Lavigne, C., Jacques, H., & Marette, A. (2001). Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C (zeta/lambda) activities. Diabetes, 50(8), 1901–1910.

    Article  PubMed  CAS  Google Scholar 

  27. Kotani, K., Ogawa, W., Matsumoto, M., et al. (1998). Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. Molecular and Cellular Biology, 18(12), 6971–6982.

    PubMed  CAS  Google Scholar 

  28. Inoki, K., Li, Y., Zhu, T., Wu, J., Guan, K. L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mtor signalling. Nature Cell Biology, 4(9), 648–657.

    Article  PubMed  CAS  Google Scholar 

  29. Inoki, K., Li, Y., Xu, T., & Guan, K. L. (2003). Rheb gtpase is a direct target of TSC2 GAP activity and regulates mtor signaling. Genes & Development, 17(15), 1829–1834.

    Article  CAS  Google Scholar 

  30. Cross, D. A., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995). Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 378(6559), 785–789.

    Article  PubMed  CAS  Google Scholar 

  31. McManus, E. J., Sakamoto, K., Armit, L. J., et al. (2005). Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. The EMBO journal, 24(8), 1571–1583.

    Article  PubMed  CAS  Google Scholar 

  32. Patel, S., Doble, B. W., MacAulay, K., Sinclair, E. M., Drucker, D. J., & Woodgett, J. R. (2008). Tissue-specific role of glycogen synthase kinase 3beta in glucose homeostasis and insulin action. Molecular and Cellular Biology, 28(20), 6314–6328.

    Article  PubMed  CAS  Google Scholar 

  33. MacAulay, K., Doble, B. W., Patel, S., et al. (2007). Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Cell Metabolism, 6(4), 329–337.

    Article  PubMed  CAS  Google Scholar 

  34. Ishikura, S., Bilan, P. J., & Klip, A. (2007). Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells. Biochemical and Biophysical Research Communications, 353(4), 1074–1079.

    Article  PubMed  CAS  Google Scholar 

  35. Accili, D., & Arden, K. C. (2004). Foxos at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 117(4), 421–426.

    Article  PubMed  CAS  Google Scholar 

  36. Puigserver, P., Rhee, J., Donovan, J., et al. (2003). Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature, 423(6939), 550–555.

    Article  PubMed  CAS  Google Scholar 

  37. Foufelle, F., & Ferre, P. (2002). New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. The Biochemical Journal, 366(Pt 2), 377–391.

    Article  PubMed  CAS  Google Scholar 

  38. Kodama, S., Koike, C., Negishi, M., & Yamamoto, Y. (2004). Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Molecular and cellular biology, 24(18), 7931–7940.

    Article  PubMed  CAS  Google Scholar 

  39. Zhang, W., Patil, S., Chauhan, B., et al. (2006). Foxo1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. The Journal of biological chemistry, 281(15), 10105–10117.

    Article  PubMed  CAS  Google Scholar 

  40. Samuel, V. T., Choi, C. S., Phillips, T. G., et al. (2006). Targeting foxo1 in mice using antisense oligonucleotide improves hepatic and peripheral insulin action. Diabetes, 55(7), 2042–2050.

    Article  PubMed  CAS  Google Scholar 

  41. Kamagate, A., Qu, S., Perdomo, G., et al. (2008). Foxo1 mediates insulin-dependent regulation of hepatic VLDL production in mice. The Journal of Clinical Investigation, 118(6), 2347–2364.

    PubMed  CAS  Google Scholar 

  42. Altomonte, J., Cong, L., Harbaran, S., et al. (2004). Foxo1 mediates insulin action on apoc-III and triglyceride metabolism. The Journal of Clinical Investigation, 114(10), 1493–1503.

    PubMed  CAS  Google Scholar 

  43. Biddinger, S. B., Haas, J. T., Yu, B. B., et al. (2008). Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nature Medicine, 14(7), 778–782.

    Article  PubMed  CAS  Google Scholar 

  44. Graf, G. A., Yu, L., Li, W. P., et al. (2003). ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. The Journal of Biological Chemistry, 278(48), 48275–48282.

    Article  PubMed  CAS  Google Scholar 

  45. Li, T., Kong, X., Owsley, E., Ellis, E., Strom, S., & Chiang, J. Y. (2006). Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. The Journal of Biological Chemistry, 281(39), 28745–28754.

    Article  PubMed  CAS  Google Scholar 

  46. Gross, D. N., van den Heuvel, A. P., & Birnbaum, M. J. (2008). The role of foxo in the regulation of metabolism. Oncogene, 27(16), 2320–2336.

    Article  PubMed  CAS  Google Scholar 

  47. Wolfrum, C., Asilmaz, E., Luca, E., Friedman, J. M., & Stoffel, M. (2004). Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature, 432(7020), 1027–1032.

    Article  PubMed  CAS  Google Scholar 

  48. Zhang, L., Rubins, N. E., Ahima, R. S., Greenbaum, L. E., & Kaestner, K. H. (2005). Foxa2 integrates the transcriptional response of the hepatocyte to fasting. Cell Metabolism, 2(2), 141–148.

    Article  PubMed  CAS  Google Scholar 

  49. Bochkis, I. M., Rubins, N. E., White, P., Furth, E. E., Friedman, J. R., & Kaestner, K. H. (2008). Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nature Medicine, 14(8), 828–836.

    Article  PubMed  CAS  Google Scholar 

  50. Horton, J. D., Goldstein, J. L., Brown, M. S. (2002). Srebps: activators of the complete program of cholesterol and fatty acid synthesis in the liver. The Journal of Clinical Investigation, 109(9), 1125–1131.

    PubMed  CAS  Google Scholar 

  51. Shimano, H., Horton, J. D., Shimomura, I., Hammer, R. E., Brown, M. S., & Goldstein, J. L. (1997). Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. The Journal of Clinical Investigation, 99(5), 846–854.

    Article  PubMed  CAS  Google Scholar 

  52. Ide, T., Shimano, H., Yahagi, N., et al. (2004). Srebps suppress IRS-2-mediated insulin signalling in the liver. Nature Cell Biology, 6(4), 351–357.

    Article  PubMed  CAS  Google Scholar 

  53. Yamamoto, T., Shimano, H., Nakagawa, Y., et al. (2004). SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes. The Journal of Biological Chemistry, 279(13), 12027–12035.

    Article  PubMed  CAS  Google Scholar 

  54. Shimomura, I., Bashmakov, Y., & Horton, J. D. (1999). Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. The Journal of Biological Chemistry, 274(42), 30028–30032.

    Article  PubMed  CAS  Google Scholar 

  55. Horton, J. D., Bashmakov, Y., Shimomura, I., & Shimano, H. (1998). Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proceedings of the National Academy of Sciences of the United States of America, 95(11), 5987–5992.

    Article  PubMed  CAS  Google Scholar 

  56. Liang, G., Yang, J., Horton, J. D., Hammer, R. E., Goldstein, J. L., & Brown, M. S. (2002). Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. The Journal of Biological Chemistry, 277(11), 9520–9528.

    Article  PubMed  CAS  Google Scholar 

  57. Repa, J. J., Liang, G., Ou, J., et al. (2000). Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, lxralpha and lxrbeta. Genes & Development, 14(22), 2819–2830.

    Article  CAS  Google Scholar 

  58. Tobin, K. A., Ulven, S. M., Schuster, G. U., et al. (2002). Liver X receptors as insulin-mediating factors in fatty acid and cholesterol biosynthesis. The Journal of Biological Chemistry, 277(12), 10691–10697.

    Article  PubMed  CAS  Google Scholar 

  59. Yabe, D., Komuro, R., Liang, G., Goldstein, J. L., & Brown, M. S. (2003). Liver-specific mrna for Insig-2 down-regulated by insulin: implications for fatty acid synthesis. Proceedings of the National Academy of Sciences of the United States of America, 100(6), 3155–3160.

    Article  PubMed  CAS  Google Scholar 

  60. Kakuma, T., Lee, Y., Higa, M., et al. (2000). Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proceedings of the National Academy of Sciences of the United States of America, 97(15), 8536–8541.

    Article  PubMed  CAS  Google Scholar 

  61. Michael, M. D., Kulkarni, R. N., Postic, C., et al. (2000). Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Molecular Cell, 6(1), 87–97.

    Article  PubMed  CAS  Google Scholar 

  62. Biddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., et al. (2008). Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metabolism, 7(2), 125–134.

    Article  PubMed  CAS  Google Scholar 

  63. Sparks, J. D., & Sparks, C. E. (1994). Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion. Biochimica et Biophysica Acta, 1215(1–2), 9–32.

    PubMed  CAS  Google Scholar 

  64. Shaffer, E. A., & Small, D. M. (1977). Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. The Journal of Clinical Investigation, 59(5), 828–840.

    Article  PubMed  CAS  Google Scholar 

  65. Dong, X. C., Copps, K. D., Guo, S., et al. (2008). Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metabolism, 8(1), 65–76.

    Article  PubMed  CAS  Google Scholar 

  66. Taniguchi, C. M., Kondo, T., Sajan, M., et al. (2006). Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and pkclambda/zeta. Cell Metabolism, 3(5), 343–353.

    Article  PubMed  CAS  Google Scholar 

  67. Miyake, K., Ogawa, W., Matsumoto, M., Nakamura, T., Sakaue, H., & Kasuga, M. (2002). Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. The Journal of Clinical Investigation, 110(10), 1483–1491.

    PubMed  CAS  Google Scholar 

  68. Matsumoto, M., Ogawa, W., Akimoto, K., et al. (2003). Pkclambda in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity. The Journal of Clinical Investigation, 112(6), 935–944.

    PubMed  CAS  Google Scholar 

  69. Tilg, H., & Moschen, A. R. (2008). Inflammatory mechanisms in the regulation of insulin resistance. Molecular Medicine (Cambridge, Mass. ), 14(3–4), 222–231.

    CAS  Google Scholar 

  70. Howard, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjorbaek, C., & Flier, J. S. (2004). Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nature Medicine, 10(7), 734–738.

    Article  PubMed  CAS  Google Scholar 

  71. Nielsen, J. H., Galsgaard, E. D., Moldrup, A., et al. (2001). Regulation of beta-cell mass by hormones and growth factors. Diabetes, 50, Suppl 1:S25–29.

    Article  PubMed  CAS  Google Scholar 

  72. Verstrepen, L., Bekaert, T., Chau, T. L., Tavernier, J., Chariot, A., & Beyaert, R. (2008). TLR-4, IL-1R and TNF-R signaling to NF-kappab: variations on a common theme. Cellular and Molecular Life Sciences: CMLS, 65(19), 2964–2978.

    Article  PubMed  CAS  Google Scholar 

  73. Shoelson, S. E., Lee, J., & Yuan, M. (2003). Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 27, Suppl 3:S49–52.

    Article  CAS  Google Scholar 

  74. Holland, W. L., Knotts, T. A., Chavez, J. A., Wang, L. P., Hoehn, K. L., & Summers, S. A. (2007). Lipid mediators of insulin resistance. Nutrition reviews, 65(6 Pt 2), S39–46.

    Article  PubMed  Google Scholar 

  75. Gao, Z., Zhang, X., Zuberi, A., et al. (2004). Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Molecular Endocrinology (Baltimore, Md. ), 18(8), 2024–2034.

    Article  CAS  Google Scholar 

  76. Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007). Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiological Reviews, 87(2), 507–520.

    Article  PubMed  CAS  Google Scholar 

  77. Malhotra, J. D., & Kaufman, R. J. (2007). The endoplasmic reticulum and the unfolded protein response. Seminars in Cell & Developmental Biology, 18(6), 716–731.

    Article  CAS  Google Scholar 

  78. Buse, M. G. (2006). Hexosamines, insulin resistance, and the complications of diabetes: current status. American Journal of Physiology. Endocrinology and Metabolism, 290(1), E1-E8.

    Article  PubMed  CAS  Google Scholar 

  79. Srinivasan, V., Tatu, U., Mohan, V., & Balasubramanyam, M. (2009). Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells. Molecular and Cellular Biochemistry, 328(1–2), 217–224.

    Article  PubMed  CAS  Google Scholar 

  80. Miele, C., Riboulet, A., Maitan, M. A., et al. (2003). Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase C alpha-mediated mechanism. The Journal of Biological Chemistry, 278(48), 47376–47387.

    Article  PubMed  CAS  Google Scholar 

  81. Frojdo, S., Vidal, H., & Pirola, L. (2009). Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans. Biochimica et Biophysica Acta, 1792(2), 83–92.

    PubMed  Google Scholar 

  82. Semple, R. K., Sleigh, A., Murgatroyd, P. R., et al. (2009). Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. The Journal of Clinical Investigation, 119(2), 315–322.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded in part by National Institutes of Health grants DK063696 and DK083697 (SBB). Because of space limitations, we were unable to include all of the references we would have liked. We apologize to our many colleagues whose work is not directly cited.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Children’s Hospital Boston, MA, Boston, USA

    Sudha B. Biddinger

Authors
  1. Sudha B. Biddinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brice Emanuelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sudha B. Biddinger .

Editor information

Editors and Affiliations

  1. School of Medicine, Div. Endocrinology, Diabetes, &, University of Pennsylvania, Curie Blvd. 415, Philadelphia, 19104, Pennsylvania, USA

    Rexford S. Ahima

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Biddinger, S.B., Emanuelli, B. (2011). Insulin Resistance in the Metabolic Syndrome. In: Ahima, R. (eds) Metabolic Basis of Obesity. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1607-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1607-5_10

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1606-8

  • Online ISBN: 978-1-4419-1607-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation