Skip to main content
NCBI home page
Journal of the Royal Society of Medicine logoLink to Journal of the Royal Society of Medicine
. 2002;95(Suppl 42):8–13.

Cellular mechanism of insulin resistance in skeletal muscle.

Kitt Falk Petersen 1, Gerald I Shulman 1
PMCID: PMC1308947  PMID: 12216329

Full Text

The Full Text of this article is available as a PDF (276.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguirre V., Uchida T., Yenush L., Davis R., White M. F. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000 Mar 24;275(12):9047–9054. doi: 10.1074/jbc.275.12.9047. [DOI] [PubMed] [Google Scholar]
  2. Cline G. W., Petersen K. F., Krssak M., Shen J., Hundal R. S., Trajanoski Z., Inzucchi S., Dresner A., Rothman D. L., Shulman G. I. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med. 1999 Jul 22;341(4):240–246. doi: 10.1056/NEJM199907223410404. [DOI] [PubMed] [Google Scholar]
  3. Dresner A., Laurent D., Marcucci M., Griffin M. E., Dufour S., Cline G. W., Slezak L. A., Andersen D. K., Hundal R. S., Rothman D. L. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest. 1999 Jan;103(2):253–259. doi: 10.1172/JCI5001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Griffin M. E., Marcucci M. J., Cline G. W., Bell K., Barucci N., Lee D., Goodyear L. J., Kraegen E. W., White M. F., Shulman G. I. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999 Jun;48(6):1270–1274. doi: 10.2337/diabetes.48.6.1270. [DOI] [PubMed] [Google Scholar]
  5. Jensen Michael D. Adipose tissue and fatty acid metabolism in humans. J R Soc Med. 2002;95 (Suppl 42):3–7. [PMC free article] [PubMed] [Google Scholar]
  6. Kim J. K., Gavrilova O., Chen Y., Reitman M. L., Shulman G. I. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem. 2000 Mar 24;275(12):8456–8460. doi: 10.1074/jbc.275.12.8456. [DOI] [PubMed] [Google Scholar]
  7. Kim J. K., Kim Y. J., Fillmore J. J., Chen Y., Moore I., Lee J., Yuan M., Li Z. W., Karin M., Perret P. Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001 Aug;108(3):437–446. doi: 10.1172/JCI11559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Krssak M., Falk Petersen K., Dresner A., DiPietro L., Vogel S. M., Rothman D. L., Roden M., Shulman G. I. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999 Jan;42(1):113–116. doi: 10.1007/s001250051123. [DOI] [PubMed] [Google Scholar]
  9. Li J., DeFea K., Roth R. A. Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem. 1999 Apr 2;274(14):9351–9356. doi: 10.1074/jbc.274.14.9351. [DOI] [PubMed] [Google Scholar]
  10. Mayerson Adam B., Hundal Ripudaman S., Dufour Sylvie, Lebon Vincent, Befroy Douglas, Cline Gary W., Enocksson Staffan, Inzucchi Silvio E., Shulman Gerald I., Petersen Kitt F. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes. 2002 Mar;51(3):797–802. doi: 10.2337/diabetes.51.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Perseghin G., Ghosh S., Gerow K., Shulman G. I. Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study. Diabetes. 1997 Jun;46(6):1001–1009. doi: 10.2337/diab.46.6.1001. [DOI] [PubMed] [Google Scholar]
  12. Petersen K. F., Laurent D., Rothman D. L., Cline G. W., Shulman G. I. Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans. J Clin Invest. 1998 Mar 15;101(6):1203–1209. doi: 10.1172/JCI579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  14. Roden M., Perseghin G., Petersen K. F., Hwang J. H., Cline G. W., Gerow K., Rothman D. L., Shulman G. I. The roles of insulin and glucagon in the regulation of hepatic glycogen synthesis and turnover in humans. J Clin Invest. 1996 Feb 1;97(3):642–648. doi: 10.1172/JCI118460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rothman D. L., Magnusson I., Cline G., Gerard D., Kahn C. R., Shulman R. G., Shulman G. I. Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):983–987. doi: 10.1073/pnas.92.4.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rothman D. L., Shulman R. G., Shulman G. I. 31P nuclear magnetic resonance measurements of muscle glucose-6-phosphate. Evidence for reduced insulin-dependent muscle glucose transport or phosphorylation activity in non-insulin-dependent diabetes mellitus. J Clin Invest. 1992 Apr;89(4):1069–1075. doi: 10.1172/JCI115686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shulman G. I. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171–176. doi: 10.1172/JCI10583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shulman G. I., Rothman D. L., Jue T., Stein P., DeFronzo R. A., Shulman R. G. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med. 1990 Jan 25;322(4):223–228. doi: 10.1056/NEJM199001253220403. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press

RESOURCES