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. 1992 Jul 1;285(Pt 1):269–274. doi: 10.1042/bj2850269

Effects of insulin-like growth factor I on the rates of glucose transport and utilization in rat skeletal muscle in vitro.

G Dimitriadis 1, M Parry-Billings 1, S Bevan 1, D Dunger 1, T Piva 1, U Krause 1, G Wegener 1, E A Newsholme 1
PMCID: PMC1132776  PMID: 1637311

Abstract

1. The effects of insulin-like growth factor I (IGF-I) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. IGF-I increased the rates of glucose transport, lactate formation, glycogen synthesis and the flux of glucose to hexose monophosphate, but it had no effect on the rate of glucose oxidation or glycogenolysis. 2. In the absence of insulin, low levels of IGF-I (0-30 ng/ml) increased the rate of glycolysis and the content of fructose 2,6-bisphosphate, but the content of glucose 6-phosphate remained unaltered; at higher levels of IGF-I (300-3000 ng/ml) the rate of glycolysis and the content of fructose 2,6-bisphosphate showed a further modest increase, but the content of glucose 6-phosphate doubled. Similar changes were seen when the level of insulin was increased from basal (0-0.4 ng/ml) to maximal (40 ng/ml). 3. Neither IGF-I nor insulin affected the contents of ATP, ADP, AMP, phosphocreatine or citrate. 4. Maximal concentrations of IGF-I increased the rate of lactate formation to a greater extent than did maximal concentrations of insulin. 5. In the presence of IGF-I, the rate of glucose utilization was less responsive to insulin. 6. The results suggest that, in rat skeletal muscle: (a) IGF-I increases the rates of glucose transport and utilization independently of insulin, and has a preferential effect on the rate of lactate formation; (b) the effects of IGF-I and insulin are not additive; (c) in addition to its effects on glucose transport, IGF-I increases the rate of glycogen synthesis and may stimulate glycolysis at the level of 6-phosphofructokinase; (d) changes in the content of fructose 2,6-bisphosphate may be part of the mechanism to regulate glycolytic flux in skeletal muscle in response to either IGF-I or insulin.

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Selected References

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  1. Bolinder J., Lindblad A., Engfeldt P., Arner P. Studies of acute effects of insulin-like growth factors I and II in human fat cells. J Clin Endocrinol Metab. 1987 Oct;65(4):732–737. doi: 10.1210/jcem-65-4-732. [DOI] [PubMed] [Google Scholar]
  2. Challiss R. A., Arch J. R., Newsholme E. A. The rate of substrate cycling between fructose 6-phosphate and fructose 1,6-bisphosphate in skeletal muscle. Biochem J. 1984 Jul 1;221(1):153–161. doi: 10.1042/bj2210153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crettaz M., Prentki M., Zaninetti D., Jeanrenaud B. Insulin resistance in soleus muscle from obese Zucker rats. Involvement of several defective sites. Biochem J. 1980 Feb 15;186(2):525–534. doi: 10.1042/bj1860525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cuendet G. S., Loten E. G., Jeanrenaud B., Renold A. E. Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice. J Clin Invest. 1976 Nov;58(5):1078–1088. doi: 10.1172/JCI108559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000–1007. doi: 10.2337/diab.30.12.1000. [DOI] [PubMed] [Google Scholar]
  6. Dimitriadis G. D., Leighton B., Parry-Billings M., West D., Newsholme E. A. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J. 1989 Jan 15;257(2):369–373. doi: 10.1042/bj2570369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dohm G. L., Elton C. W., Raju M. S., Mooney N. D., DiMarchi R., Pories W. J., Flickinger E. G., Atkinson S. M., Jr, Caro J. F. IGF-I--stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM. Diabetes. 1990 Sep;39(9):1028–1032. doi: 10.2337/diab.39.9.1028. [DOI] [PubMed] [Google Scholar]
  8. Espinal J., Dohm G. L., Newsholme E. A. Sensitivity to insulin of glycolysis and glycogen synthesis of isolated soleus-muscle strips from sedentary, exercised and exercise-trained rats. Biochem J. 1983 May 15;212(2):453–458. doi: 10.1042/bj2120453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Giacca A., Gupta R., Efendic S., Hall K., Skottner A., Lickley L., Vranic M. Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs. Diabetes. 1990 Mar;39(3):340–347. doi: 10.2337/diab.39.3.340. [DOI] [PubMed] [Google Scholar]
  10. Guler H. P., Zapf J., Froesch E. R. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987 Jul 16;317(3):137–140. doi: 10.1056/NEJM198707163170303. [DOI] [PubMed] [Google Scholar]
  11. Hammerstedt R. H. A rapid method for isolating glucose metabolites involved in substrate cycling. Anal Biochem. 1980 Dec;109(2):443–448. doi: 10.1016/0003-2697(80)90675-2. [DOI] [PubMed] [Google Scholar]
  12. Hers H. G., Van Schaftingen E. Fructose 2,6-bisphosphate 2 years after its discovery. Biochem J. 1982 Jul 15;206(1):1–12. doi: 10.1042/bj2060001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacob R., Barrett E., Plewe G., Fagin K. D., Sherwin R. S. Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. Comparison with insulin. J Clin Invest. 1989 May;83(5):1717–1723. doi: 10.1172/JCI114072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kern P. A., Svoboda M. E., Eckel R. H., Van Wyk J. J. Insulinlike growth factor action and production in adipocytes and endothelial cells from human adipose tissue. Diabetes. 1989 Jun;38(6):710–717. doi: 10.2337/diab.38.6.710. [DOI] [PubMed] [Google Scholar]
  15. Klip A., Ramlal T., Young D. A., Holloszy J. O. Insulin-induced translocation of glucose transporters in rat hindlimb muscles. FEBS Lett. 1987 Nov 16;224(1):224–230. doi: 10.1016/0014-5793(87)80452-0. [DOI] [PubMed] [Google Scholar]
  16. Leighton B., Budohoski L., Lozeman F. J., Challiss R. A., Newsholme E. A. The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat. Biochem J. 1985 Apr 1;227(1):337–340. doi: 10.1042/bj2270337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Meuli C., Froesch E. R. Insulin and nonsuppressible insulin-like activity (NSILA-S) stimulate the same glucose transport system via two separate receptors in rat heart. Biochem Biophys Res Commun. 1977 Apr 11;75(3):689–695. doi: 10.1016/0006-291x(77)91527-3. [DOI] [PubMed] [Google Scholar]
  18. Poggi C., Le Marchand-Brustel Y., Zapf J., Froesch E. R., Freychet P. Effects and binding of insulin-like growth factor I in the isolated soleus muscle of lean and obese mice: comparison with insulin. Endocrinology. 1979 Sep;105(3):723–730. doi: 10.1210/endo-105-3-723. [DOI] [PubMed] [Google Scholar]
  19. Rinderknecht E., Humbel R. E. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978 Apr 25;253(8):2769–2776. [PubMed] [Google Scholar]
  20. Rossetti L., Frontoni S., Dimarchi R., DeFronzo R. A., Giaccari A. Metabolic effects of IGF-I in diabetic rats. Diabetes. 1991 Apr;40(4):444–448. doi: 10.2337/diab.40.4.444. [DOI] [PubMed] [Google Scholar]
  21. Rossetti L., Giaccari A. Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake. A dose-response euglycemic clamp study in normal and diabetic rats. J Clin Invest. 1990 Jun;85(6):1785–1792. doi: 10.1172/JCI114636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schoenle E., Zapf J., Froesch E. R. Effects of insulin and NSILA on adipocytes of normal and diabetic rats: receptor binding, glucose transport and glucose metabolism. Diabetologia. 1977 May;13(3):243–249. doi: 10.1007/BF01219707. [DOI] [PubMed] [Google Scholar]
  23. Schoenle E., Zapf J., Humbel R. E., Froesch E. R. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. doi: 10.1038/296252a0. [DOI] [PubMed] [Google Scholar]
  24. Sinha M. K., Buchanan C., Leggett N., Martin L., Khazanie P. G., Dimarchi R., Pories W. J., Caro J. F. Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport. Diabetes. 1989 Oct;38(10):1217–1225. doi: 10.2337/diab.38.10.1217. [DOI] [PubMed] [Google Scholar]
  25. Uthne K., Reagan C. R., Gimpel L. P., Kostyo J. L. Effects of human somatomedin preparations on membrane transport and protein synthesis in the isolated rat diaphragm. J Clin Endocrinol Metab. 1974 Sep;39(3):548–554. doi: 10.1210/jcem-39-3-548. [DOI] [PubMed] [Google Scholar]
  26. Wegener G., Krause U., Thuy M. Fructose 2,6-bisphosphate and glycolytic flux in skeletal muscle of swimming frog. FEBS Lett. 1990 Jul 16;267(2):257–260. doi: 10.1016/0014-5793(90)80939-g. [DOI] [PubMed] [Google Scholar]
  27. Young D. A., Uhl J. J., Cartee G. D., Holloszy J. O. Activation of glucose transport in muscle by prolonged exposure to insulin. Effects of glucose and insulin concentrations. J Biol Chem. 1986 Dec 5;261(34):16049–16053. [PubMed] [Google Scholar]
  28. Yu K. T., Czech M. P. The type I insulin-like growth factor receptor mediates the rapid effects of multiplication-stimulating activity on membrane transport systems in rat soleus muscle. J Biol Chem. 1984 Mar 10;259(5):3090–3095. [PubMed] [Google Scholar]
  29. Zapf J., Hauri C., Waldvogel M., Froesch E. R. Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomized rats. J Clin Invest. 1986 Jun;77(6):1768–1775. doi: 10.1172/JCI112500. [DOI] [PMC free article] [PubMed] [Google Scholar]

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