Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1980 Mar 15;186(3):733–738. doi: 10.1042/bj1860733

Prolonged effect of insulin on glucose uptake by rat skeletal muscle

Stephen B Lewis *, Thomas A Schultz *, Ellen L Daniels *, Michael M Bliziotes *, William Montague †
PMCID: PMC1161708  PMID: 6994713

Abstract

The fate of insulin, as it relates to its action on skeletal-muscle glucose uptake, was studied in non-cyclically perfused rat hindlimbs. Insulin (1m-i.u./ml) with and without 125I-labelled insulin was infused intra-arterially for 5 or 6min. Net glucose uptake and the release of 125I-labelled insulin into the venous effluent were evaluated by arteriovenous-difference measurements for an additional 24–32min. The infusion of insulin for 5min promoted glucose uptake, an effect that persisted throughout a subsequent 25min of perfusion in the absence of insulin. The addition of insulin antibody to the perfusate in the presence of insulin blocked the action of insulin on glucose uptake, but it failed to alter insulin action if the muscle tissue had been exposed to insulin before addition of antibody. When 125I-labelled albumin was infused for 6min, venous effluent radioactivity decayed rapidly and remained HClO4-insoluble and there was no significant tissue retension of radioactivity. Comparable experiments in which 125I-labelled insulin was infused for 6min revealed that the venous effluent radioactivity decayed more slowly, a significant amount of the 125I-labelled insulin appeared as fragments (HClO4-soluble) and there was a significant retention of radioactivity in the tissue. Radioactivity in muscle tissue biopsies obtained 28min after infusion of 125I-labelled insulin was associated largely with intact insulin and a peptide of mol.wt. 2400. The total radioactivity retained in the muscle at this time was 7% of the amount infused. An insulin bolus (1i.u.) failed to increase the discharge of this tissue-associated radioactivity. These results suggest that insulin and a product of insulin metabolism persists in muscle tissue long after the arterial presence of insulin ends. This tissue residence and processing of insulin may be important components of insulin's prolonged action on glucose uptake by skeletal muscle.

Full text

PDF
733

Selected References

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

  1. Bomboy J. D., Jr, Lewis S. B., Lacy W. W., Sinclair-Smith B. C., Liljenquist J. E. Transient stimulatory effect of sustained hyperglucagonemia on splanchnic glucose production in normal and diabetic man. Diabetes. 1977 Mar;26(3):177–174. doi: 10.2337/diab.26.3.177. [DOI] [PubMed] [Google Scholar]
  2. Brush J. S., Kitabchi A. E. Metabolic disposition of [131I] iodoinsulin within the rat diaphragm. Biochim Biophys Acta. 1970 Jul 21;215(1):134–144. doi: 10.1016/0304-4165(70)90396-x. [DOI] [PubMed] [Google Scholar]
  3. Brush J. S. Purification and characterizatoion of a protease with specificity for insulin from rat muscle. Diabetes. 1971 Mar;20(3):140–145. [PubMed] [Google Scholar]
  4. Carpentier J. L., Gorden P., Freychet P., Le Cam A., Orci L. Lysosomal association of internalized 125I-insulin in isolated rat hepatocytes. Direct demonstration by quantitative electron microscopic autoradiography. J Clin Invest. 1979 Jun;63(6):1249–1261. doi: 10.1172/JCI109420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chandler M. L., Varandani P. T. Kinetic analysis of the mechanism of insulin degradation by glutathione-insulin transhydrogenase (thiol: protein-disulfide oxidoreductase). Biochemistry. 1975 May 20;14(10):2107–2115. doi: 10.1021/bi00681a010. [DOI] [PubMed] [Google Scholar]
  6. Cuatrecasas P. Insulin--receptor interactions in adipose tissue cells: direct measurement and properties. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1264–1268. doi: 10.1073/pnas.68.6.1264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freychet P., Kahn R., Roth J., Neville D. M., Jr Insulin interactions with liver plasma membranes. Independence of binding of the hormone and its degradation. J Biol Chem. 1972 Jun 25;247(12):3953–3961. [PubMed] [Google Scholar]
  8. Freychet P., Roth J., Neville D. M., Jr Monoiodoinsulin: demonstration of its biological activity and binding to fat cells and liver membranes. Biochem Biophys Res Commun. 1971 Apr 16;43(2):400–408. doi: 10.1016/0006-291x(71)90767-4. [DOI] [PubMed] [Google Scholar]
  9. Goldfine I. D. Insulin receptors and the site of action of insulin. Life Sci. 1978 Dec 31;23(27-28):2639–2648. doi: 10.1016/0024-3205(78)90643-4. [DOI] [PubMed] [Google Scholar]
  10. Goldfine I. D., Jones A. L., Hradek G. T., Wong K. Y., Mooney J. S. Entry of insulin into human cultured lymphocytes: electron microscope autoradiographic analysis. Science. 1978 Nov 17;202(4369):760–763. doi: 10.1126/science.715440. [DOI] [PubMed] [Google Scholar]
  11. Gorden P., Carpentier J. L., Freychet P., LeCam A., Orci L. Intracellular translocation of iodine-125-labeled insulin: direct demonstration in isolated hepatocytes. Science. 1978 May 19;200(4343):782–785. doi: 10.1126/science.644321. [DOI] [PubMed] [Google Scholar]
  12. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  13. Hamlin J. L., Arquilla E. R. Monoiodoinsulin. Preparation, purification, and characterization of a biologically active derivative substituted predominantly on tyrosine A14. J Biol Chem. 1974 Jan 10;249(1):21–32. [PubMed] [Google Scholar]
  14. Izzo J. L., Bartlett J. W., Roncone A., Izzo M. J., Bale W. F. Physiological processes and dynamics in the disposition of small and large doses of biologically active and inactive 131-I-insulins in the rat. J Biol Chem. 1967 May 25;242(10):2343–2355. [PubMed] [Google Scholar]
  15. Kahn C. R., Baird K. The fate of insulin bound to adipocytes. Evidence for compartmentalization and processing. J Biol Chem. 1978 Jul 25;253(14):4900–4906. [PubMed] [Google Scholar]
  16. Lewis S. B., Schultz T. A., Westbie D. K., Gerich J. E., Wallin J. D. Insulin-glucose dynamics during flow-through perfusion of the isolated rat hindlimb. Horm Metab Res. 1977 May;9(3):190–195. doi: 10.1055/s-0028-1093534. [DOI] [PubMed] [Google Scholar]
  17. Pastan I., Roth J., Macchia V. Binding of hormone to tissue: the first step in polypeptide hormone action. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1802–1809. doi: 10.1073/pnas.56.6.1802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Phelps B. H., Varandani P. T., Shroyer L. A. Insulin B chain-degrading neutral peptidase activity in the rat. Tissue distribution and the effects of starvation and streptozotocin-induced diabetes. Arch Biochem Biophys. 1979 Jun;195(1):1–11. doi: 10.1016/0003-9861(79)90321-7. [DOI] [PubMed] [Google Scholar]
  19. Schultz T. A., Lewis S. B., Westbie D. K., Wallin J. D., Gerich J. E. Glucose delivery: a modulator of glucose uptake in contracting skeletal muscle. Am J Physiol. 1977 Dec;233(6):E514–E518. doi: 10.1152/ajpendo.1977.233.6.E514. [DOI] [PubMed] [Google Scholar]
  20. Steiner D. F. The Banting Memorial Lecture 1976. Insulin today. Diabetes. 1977 Apr;26(4):322–340. doi: 10.2337/diab.26.4.322. [DOI] [PubMed] [Google Scholar]
  21. Terris S., Steiner D. F. Binding and degradation of 125I-insulin by rat hepatocytes. J Biol Chem. 1975 Nov 10;250(21):8389–8398. [PubMed] [Google Scholar]
  22. Terris S., Steiner D. F. Retention and degradation of 125I-insulin by perfused livers from diabetic rats. J Clin Invest. 1976 Apr;57(4):885–896. doi: 10.1172/JCI108365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Varandani P. T. Insulin degradation. X. Identification of insulin degrading activity of rat liver plasma membrane as glutathione-insulin transhydrogenase. Biochem Biophys Res Commun. 1973 Dec 10;55(3):689–696. doi: 10.1016/0006-291x(73)91199-6. [DOI] [PubMed] [Google Scholar]
  24. Weitzel G., Eisele K., Guglielmi H., Stock W., Renner R. Structure and activity of insulin. XI. Biologically active synthetic peptides of the insulin sequence B22-25. Hoppe Seylers Z Physiol Chem. 1971 Dec;352(12):1735–1738. [PubMed] [Google Scholar]
  25. Weitzel G., Eisele K., Schulz V., Stock W. Structure and activity of insulin. XII. Further studies on biologically acitve synthetic fragments of the B-chain. Hoppe Seylers Z Physiol Chem. 1973 Mar;354(3):321–330. doi: 10.1515/bchm2.1973.354.1.321. [DOI] [PubMed] [Google Scholar]
  26. Wohltmann H. J., Narahara H. T. Inability of anti-insulin serum to neutralize insulin after the hormone has become bound to muscle. Biochim Biophys Acta. 1967 Feb 1;135(1):173–175. doi: 10.1016/0005-2736(67)90023-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES