Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Feb 1;265(3):887–890. doi: 10.1042/bj2650887

The effect of fasting on the activation in vivo of the insulin receptor kinase.

I Contreras 1, G L Dohm 1, S Abdallah 1, J A Wells 1, N Mooney 1, A Rovira 1, J F Caro 1
PMCID: PMC1133714  PMID: 2407238

Abstract

Fasting causes insulin resistance in liver and fat, and increases insulin sensitivity in muscle. We studied the response in vitro and in vivo to insulin of the insulin receptor tyrosine kinase in muscle and liver from 72 h fasted and control rats. Insulin was injected intraperitoneally together with glucose, and blood and tissue samples were obtained 0, 5, 15 and 30 min later. Basal serum glucose and insulin levels were significantly higher in control than in fasting rats. Serum glucose rose to approximately 300 mg/dl at 5 min and then progressively declined without hypoglycaemia. Receptors were prepared from whole tissue by wheat germ lectin affinity chromatography. 125I-insulin binding to purified receptors was increased by fasting in both muscle (18%) and liver (50%). In untreated fasting and control animals, muscle and liver insulin receptor tyrosine kinase activity was stimulated to similar levels by insulin added in vitro. With only insulin treatment in vivo, muscle receptor tyrosine kinase behaved similarly in fasting and control animals with maximal activation at 15 min post injection. In liver, insulin in vivo stimulated receptor tyrosine kinase activity maximally at 5 min post injection in both fasting and control, but in fasting animals the treatment in vivo caused a significantly larger and more prolonged activation of the enzymic activity, possibly due to a decrease in the rate of dephosphorylation and deactivation of the beta subunits.

Full text

PDF
887

Selected References

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

  1. Arner P., Einarsson K., Ewerth S., Livingston J. Studies of the human liver insulin receptor in noninsulin-dependent diabetes mellitus. J Clin Invest. 1986 May;77(5):1716–1718. doi: 10.1172/JCI112492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Backer J. M., Kahn C. R., White M. F. Tyrosine phosphorylation of the insulin receptor during insulin-stimulated internalization in rat hepatoma cells. J Biol Chem. 1989 Jan 25;264(3):1694–1701. [PubMed] [Google Scholar]
  3. Bergeron J. J., Lai W. H., Kay D. G., Doherty J. J., 2nd, Khan M. N., Posner B. I. The endosomal apparatus and transmembrane signalling. Adv Exp Med Biol. 1988;234:213–224. doi: 10.1007/978-1-4757-1980-2_14. [DOI] [PubMed] [Google Scholar]
  4. Blackshear P. J., Nemenoff R. A., Avruch J. Characteristics of insulin and epidermal growth factor stimulation of receptor autophosphorylation in detergent extracts of rat liver and transplantable rat hepatomas. Endocrinology. 1984 Jan;114(1):141–152. doi: 10.1210/endo-114-1-141. [DOI] [PubMed] [Google Scholar]
  5. Brady L. J., Goodman M. N., Kalish F. N., Ruderman N. B. Insulin binding and sensitivity in rat skeletal muscle: effect of starvation. Am J Physiol. 1981 Feb;240(2):E184–E190. doi: 10.1152/ajpendo.1981.240.2.E184. [DOI] [PubMed] [Google Scholar]
  6. Caro J. F., Amatruda J. M. The regulation of lipid synthesis in freshly isolated and primary cultures of hepatocytes from fasted rats: the primary role of insulin. Metabolism. 1982 Jan;31(1):14–18. [PubMed] [Google Scholar]
  7. Caro J. F., Sinha M. K., Raju S. M., Ittoop O., Pories W. J., Flickinger E. G., Meelheim D., Dohm G. L. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. J Clin Invest. 1987 May;79(5):1330–1337. doi: 10.1172/JCI112958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cech J. M., Freeman R. B., Jr, Caro J. F., Amatruda J. M. Insulin action and binding in isolated hepatocytes from fasted, streptozotocin-diabetic, and older, spontaneously obese rats. Biochem J. 1980 Jun 15;188(3):839–845. doi: 10.1042/bj1880839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Contreras I., Caro J. The collisional hypothesis of insulin action, receptor internalization and diabetes. Trends Biochem Sci. 1989 Oct;14(10):399–399. doi: 10.1016/0968-0004(89)90285-5. [DOI] [PubMed] [Google Scholar]
  10. Czech M. P. The nature and regulation of the insulin receptor: structure and function. Annu Rev Physiol. 1985;47:357–381. doi: 10.1146/annurev.ph.47.030185.002041. [DOI] [PubMed] [Google Scholar]
  11. Freidenberg G. R., Henry R. R., Klein H. H., Reichart D. R., Olefsky J. M. Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects. J Clin Invest. 1987 Jan;79(1):240–250. doi: 10.1172/JCI112789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Freidenberg G. R., Klein H. H., Cordera R., Olefsky J. M. Insulin receptor kinase activity in rat liver. Regulation by fasting and high carbohydrate feeding. J Biol Chem. 1985 Oct 15;260(23):12444–12453. [PubMed] [Google Scholar]
  13. Gherzi R., Andraghetti G., Ferrannini E., Cordera R. Insulin receptor autophosphorylation and kinase activity in streptozotocin diabetic rats. Effect of a short fast. Biochem Biophys Res Commun. 1986 Nov 14;140(3):850–856. doi: 10.1016/0006-291x(86)90712-6. [DOI] [PubMed] [Google Scholar]
  14. Goldfine I. D. The insulin receptor: molecular biology and transmembrane signaling. Endocr Rev. 1987 Aug;8(3):235–255. doi: 10.1210/edrv-8-3-235. [DOI] [PubMed] [Google Scholar]
  15. Goodman M. N., Ruderman N. B. Insulin sensitivity of rat skeletal muscle: effects of starvation and aging. Am J Physiol. 1979 May;236(5):E519–E523. doi: 10.1152/ajpendo.1979.236.5.E519. [DOI] [PubMed] [Google Scholar]
  16. Harikumar P., Ninjoor V. Response of heterogenous rat liver lysosome populations to starvation and refeeding. Biochim Biophys Acta. 1979 Sep 20;587(1):60–66. doi: 10.1016/0304-4165(79)90220-4. [DOI] [PubMed] [Google Scholar]
  17. Kahn B. B., Simpson I. A., Cushman S. W. Divergent mechanisms for the insulin resistant and hyperresponsive glucose transport in adipose cells from fasted and refed rats. Alterations in both glucose transporter number and intrinsic activity. J Clin Invest. 1988 Aug;82(2):691–699. doi: 10.1172/JCI113649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kahn C. R., White M. F. The insulin receptor and the molecular mechanism of insulin action. J Clin Invest. 1988 Oct;82(4):1151–1156. doi: 10.1172/JCI113711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kasperek G. J., Dohm G. L., Tapscott E. B., Powell T. Effect of exercise on liver protein loss and lysosomal enzyme levels in fed and fasted rats. Proc Soc Exp Biol Med. 1980 Sep;164(4):430–434. doi: 10.3181/00379727-164-40890. [DOI] [PubMed] [Google Scholar]
  20. Kasuga M., Akanuma Y., Iwamoto Y., Kosaka K. Effects of fasting and refeeding of insulin receptors and glucose metabolism in rat adipocytes. Endocrinology. 1977 May;100(5):1384–1390. doi: 10.1210/endo-100-5-1384. [DOI] [PubMed] [Google Scholar]
  21. Olefsky J. M. Effects of fasting on insulin binding, glucose transport, and glucose oxidation in isolated rat adipocytes: relationships between insulin receptors and insulin action. J Clin Invest. 1976 Dec;58(6):1450–1460. doi: 10.1172/JCI108601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pokrovsky A. A., Tashev T. A., Krustev L. P., Tutelyan V. A., Kravchenko L. V. Effect of long-term starvation on the rat liver lysosomes. Int J Vitam Nutr Res. 1976;46(1):75–82. [PubMed] [Google Scholar]
  23. Pénicaud L., Kandé J., Le Magnen J., Girard J. R. Insulin action during fasting and refeeding in rat determined by euglycemic clamp. Am J Physiol. 1985 Nov;249(5 Pt 1):E514–E518. doi: 10.1152/ajpendo.1985.249.5.E514. [DOI] [PubMed] [Google Scholar]
  24. Trowbridge M., Sussman A., Ferguson L., Draznin B., Neufeld N., Begum N., Tepperman H., Tepperman J. Mechanisms of the fasting-induced dissociation of insulin binding from its action in isolated rat hepatocytes. Mol Cell Biochem. 1984 Apr;62(1):25–36. doi: 10.1007/BF00230074. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES