Skip to main content

Advertisement

Log in

Effects of resistin expression on glucose metabolism and hepatic insulin resistance

  • Original Paper
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

In order to observe the effect of increased serum resistin on glucose metabolism, insulin sensitivity, and hepatic insulin resistance (IR), mice were intravenously injected with recombinant adenovirus carrying the resistin gene (Adv-resistin-EGFP). Changes in hepatic glucose metabolism were observed using the Periodic Acid-Schiff method. Hepatic AMP-activated protein kinase (AMPK) activation was assessed by Western blot analysis, and glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was determined using real-time RT-PCR. Although no effect on fasting blood glucose was detected, increased fasting insulin levels, decreased glucose tolerance and insulin sensitivity, and reduced hepatic glycogen levels and AMPK activation were seen in the Adv-resistin-EGFP mice. Finally, elevated G6Pase and PEPCK mRNA expression levels were detected upon overexpression of resistin. Resistin may inhibit hepatic AMPK activity, which results in elevated expression of gluconeogenic enzymes thereby affecting glucose metabolism and leading to decreased glycogen storage that contributes to the development of hepatic IR.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. I.N. Holcomb, R.C. Kabakoff, B. Chan, T.W. Baker, A. Gurney, W. Henzel, C. Nelson, H.B. Lowman, B.D. Wright, N.J. Skelton, G.D. Frantz, D.B. Tumas, F.V. Peale Jr, D.L. Shelton, C.C. Hébert, FIZZI, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J. 19, 4046–4055 (2002)

    Article  Google Scholar 

  2. K.H. Kim, K. Lee, Y.S. Moon, H.S. Sul, A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J. Biol. Chem. 276, 11252–11256 (2001)

    Article  CAS  PubMed  Google Scholar 

  3. C.M. Steppan, S.T. Bailey, S. Bhat, E.J. Brown, R.R. Banerjee, C.M. Wright, H.R. Patel, R.S. Ahima, M.A. Lazar, The hormone resistin links obesity to diabetes. Nature 409, 307–312 (2001)

    Article  CAS  PubMed  Google Scholar 

  4. M.W. Rajala, Y. Qi, H.R. Patel, N. Takahashi, R. Banerjee, U.B. Pajvani, M.K. Sinha, R.L. Gingerich, P.E. Scherer, R.S. Ahima, Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 53, 1671–1679 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. Y. Kitagawa, H. Bujo, K. Takahashi, M. Shibasaki, K. Ishikawa, K. Yagui, N. Hashimoto, K. Noda, T. Nakamura, S. Yano, Y. Saito, Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin. Diabetologia 47, 1847–1853 (2004)

    Article  CAS  PubMed  Google Scholar 

  6. J.H. Lee, J.W. Bullen Jr, V.L. Stoyneva, C.S. Mantzoros, Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia. Am. J. Physiol. Endocrinol. Metab. 288, E625–E632 (2005)

    Article  CAS  PubMed  Google Scholar 

  7. C.C. Juan, L.C. Au, V.S. Fang, S.F. Kang, Y.H. Ko, S.F. Kuo, Y.P. Hsu, C.F. Kwok, L.T. Ho, Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem. Biophys. Res. Commun. 289, 1328–1333 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. H. Masuzaki, J. Paterson, H. Shinyama, N.M. Morton, J.J. Mullins, J.R. Seckl, J.S. Flier, A transgenic model of visceral obesity and the metabolic syndrome. Science 294, 2166–2170 (2001)

    Article  CAS  PubMed  Google Scholar 

  9. G. Milan, M. Granzotto, A. Scarda, A. Calcagno, C. Pagano, G. Federspil, R. Vettor, Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss. Obes. Res. 10, 1095–1103 (2002)

    Article  CAS  PubMed  Google Scholar 

  10. M.W. Rajala, S. Obici, P.E. Scherer, L. Rossetti, Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J. Clin. Invest. 111, 225–230 (2003)

    CAS  PubMed  Google Scholar 

  11. R.R. Banerjee, S.M. Rangwala, J.S. Shapiro, A.S. Rich, B. Rhoades, Y. Qi, J. Wang, M.W. Rajala, A. Pocai, P.E. Scherer, C.M. Steppan, R.S. Ahima, S. Obici, L. Rossetti, M.A. Lazar, Regulation of fasted blood glucose by resistin. Science 303, 1195–1198 (2004)

    Article  CAS  PubMed  Google Scholar 

  12. E.D. Muse, S. Obici, S. Bhanot, B.P. Monia, R.A. McKay, M.W. Rajala, P.E. Scherer, L. Rossetti, Role of resistin in diet-induced hepatic insulin resistance. J. Clin. Invest. 114, 232–239 (2004)

    CAS  PubMed  Google Scholar 

  13. H. Satoh, M.T. Nguyen, P.D. Miles, T. Imamura, I. Usui, J.M. Olefsky, Adenovirus-mediated chronic “hyper-resistinemia” leads to in vivo insulin resistance in normal rats. J. Clin. Invest. 114, 224–231 (2004)

    CAS  PubMed  Google Scholar 

  14. P.G. McTernan, C.M. Kusminski, S. Kumar, Resistin. Curr. Opin. Lipidol. 17, 170–175 (2006)

    Article  CAS  PubMed  Google Scholar 

  15. N. Sato, K. Kobayashi, T. Inoguchi, N. Sonoda, M. Imamura, N. Sekiguchi, N. Nakashima, H. Nawata, Adenovirus-mediated high expression of resistin causes dyslipidemia in mice. Endocrinology 146, 273–279 (2005)

    Article  CAS  PubMed  Google Scholar 

  16. S.M. Rangwala, A.S. Rich, B. Rhoades, J.S. Shapiro, S. Obici, L. Rossetti, M.A. Lazar, Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 53, 1937–1941 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. C.M. Steppan, M.A. Lazar, Resistin and obesity-associated insulin resistance. Trends Endocrinol. Metab. 13, 18–23 (2002)

    Article  CAS  PubMed  Google Scholar 

  18. M. Haluzik, D. Haluzikova, The role of resistin in obesity-induced insulin resistance. Curr. Opin. Investig. Drugs 7, 306–311 (2006)

    CAS  PubMed  Google Scholar 

  19. Y. Qi, Z. Nie, Y.S. Lee, N.S. Singhal, P.E. Scherer, M.A. Lazar, R.S. Ahima, Loss of resistin improves glucose homeostasis in leptin deficiency. Diabetes 55, 3083–3090 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. B. Viollet, M. Foretz, B. Guigas, S. Horman, R. Dentin, L. Bertrand, L. Hue, F. Andreelli, Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J. Physiol. 574, 41–53 (2006)

    Article  CAS  PubMed  Google Scholar 

  21. J.M. Corton, J.G. Gillespie, S.A. Hawley, D.G. Hardie, 5-aminoimidazole-4-carboxamide ribonucleoside, a specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 229, 558–565 (1995)

    Article  CAS  PubMed  Google Scholar 

  22. R. Bergeron, S.F. Previs, G.W. Cline, P. Perret, R.R. Russell 3rd, L.H. Young, G.I. Shulman, Effect of 5-aminoimidazole-4-carboxamide–1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50, 1076–1082 (2001)

    Article  CAS  PubMed  Google Scholar 

  23. M. Foretz, N. Ancellin, F. Andreelli, Y. Saintillan, P. Grondin, A. Kahn, B. Thorens, S. Vaulont, B. Viollet, Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 54, 1331–1339 (2005)

    Article  CAS  PubMed  Google Scholar 

  24. P.A. Lochhead, I.P. Salt, K.S. Walker, D.G. Hardie, C. Sutherland, 5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes 49, 896–903 (2000)

    Article  CAS  PubMed  Google Scholar 

  25. N.S. Singhal, M.A. Lazar, R.S. Ahima, Central resistin induces hepatic insulin resistance via neuropeptide Y. J. Neurosci. 27, 12924–12932 (2007)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This research was supported by the National Science Foundation of China (No. 30570886).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yan Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, FP., He, J., Li, ZZ. et al. Effects of resistin expression on glucose metabolism and hepatic insulin resistance. Endocr 35, 243–251 (2009). https://doi.org/10.1007/s12020-009-9148-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-009-9148-4

Keywords

Navigation