Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Sep;94(3):1126–1133. doi: 10.1172/JCI117427

Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans.

M A Hussain 1, O Schmitz 1, A Mengel 1, Y Glatz 1, J S Christiansen 1, J Zapf 1, E R Froesch 1
PMCID: PMC295178  PMID: 8083353

Abstract

Insulin-like growth factor-I (IGF-I) is considered to be the mediator of the growth-promoting effects of growth hormone (GH). The metabolic effects of these two hormones, however, are different. Whereas GH treatment leads to elevated insulin and glucose levels, reduced insulin sensitivity, and impaired glucose tolerance, IGF-I treatment leads to reduced insulin and GH levels and enhanced insulin sensitivity. IGF-I may, therefore, not only be the mediator of the growth-promoting effects of GH but also a modulator of the effects of GH on insulin action and glucose metabolism. To study the influence of GH and IGF-I on substrate metabolism and insulin sensitivity (assessed by euglycemic, hyperinsulinemic clamping combined with indirect calorimetry and glucose tracer infusion), we have treated eight GH-deficient adults with GH (2 IU/m2 daily subcutaneously [s.c.]), IGF-I (10 micrograms/kg.h s.c.), or both hormones together for 7 d, respectively, and compared the effects of these treatment regimens with a control phase. Our findings suggest that (a) both GH and IGF-I promote lipolysis and lipid oxidation, albeit by different mechanisms; (b) treatment with either hormone is followed by enhanced energy expenditure and reduced protein oxidation; and (c) IGF-I reverses the insulin resistance induced by GH.

Full text

PDF
1126

Selected References

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

  1. Bak J. F., Møller N., Schmitz O. Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans. Am J Physiol. 1991 May;260(5 Pt 1):E736–E742. doi: 10.1152/ajpendo.1991.260.5.E736. [DOI] [PubMed] [Google Scholar]
  2. Bar R. S., Clemmons D. R., Boes M., Busby W. H., Booth B. A., Dake B. L., Sandra A. Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart. Endocrinology. 1990 Sep;127(3):1078–1086. doi: 10.1210/endo-127-3-1078. [DOI] [PubMed] [Google Scholar]
  3. Bar R. S., Harrison L. C., Muggeo M., Gorden P., Kahn C. R., Roth J. Regulation of insulin receptors in normal and abnormal physiology in humans. Adv Intern Med. 1979;24:23–52. [PubMed] [Google Scholar]
  4. Baxter R. C., Martin J. L. Structure of the Mr 140,000 growth hormone-dependent insulin-like growth factor binding protein complex: determination by reconstitution and affinity-labeling. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6898–6902. doi: 10.1073/pnas.86.18.6898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berelowitz M., Szabo M., Frohman L. A., Firestone S., Chu L., Hintz R. L. Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science. 1981 Jun 12;212(4500):1279–1281. doi: 10.1126/science.6262917. [DOI] [PubMed] [Google Scholar]
  6. Bergman R. N., Hope I. D., Yang Y. J., Watanabe R. M., Meador M. A., Youn J. H., Ader M. Assessment of insulin sensitivity in vivo: a critical review. Diabetes Metab Rev. 1989 Aug;5(5):411–429. doi: 10.1002/dmr.5610050501. [DOI] [PubMed] [Google Scholar]
  7. Binoux M., Hossenlopp P. Insulin-like growth factor (IGF) and IGF-binding proteins: comparison of human serum and lymph. J Clin Endocrinol Metab. 1988 Sep;67(3):509–514. doi: 10.1210/jcem-67-3-509. [DOI] [PubMed] [Google Scholar]
  8. Bratusch-Marrain P. R., Smith D., DeFronzo R. A. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab. 1982 Nov;55(5):973–982. doi: 10.1210/jcem-55-5-973. [DOI] [PubMed] [Google Scholar]
  9. Caro J. F., Poulos J., Ittoop O., Pories W. J., Flickinger E. G., Sinha M. K. Insulin-like growth factor I binding in hepatocytes from human liver, human hepatoma, and normal, regenerating, and fetal rat liver. J Clin Invest. 1988 Apr;81(4):976–981. doi: 10.1172/JCI113451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DEBODO R. C., STEELE R., ALTSZULER N., DUNN A., BISHOP J. S. ON THE HORMONAL REGULATION OF CARBOHYDRATE METABOLISM; STUDIES WITH C14 GLUCOSE. Recent Prog Horm Res. 1963;19:445–488. [PubMed] [Google Scholar]
  12. DeFronzo R. A., Ferrannini E. Regulation of hepatic glucose metabolism in humans. Diabetes Metab Rev. 1987 Apr;3(2):415–459. doi: 10.1002/dmr.5610030204. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  15. Dietz J., Schwartz J. Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes. Metabolism. 1991 Aug;40(8):800–806. doi: 10.1016/0026-0495(91)90006-i. [DOI] [PubMed] [Google Scholar]
  16. Elahi D., McAloon-Dyke M., Fukagawa N. K., Sclater A. L., Wong G. A., Shannon R. P., Minaker K. L., Miles J. M., Rubenstein A. H., Vandepol C. J. Effects of recombinant human IGF-I on glucose and leucine kinetics in men. Am J Physiol. 1993 Dec;265(6 Pt 1):E831–E838. doi: 10.1152/ajpendo.1993.265.6.E831. [DOI] [PubMed] [Google Scholar]
  17. Elia M., Livesey G. Theory and validity of indirect calorimetry during net lipid synthesis. Am J Clin Nutr. 1988 Apr;47(4):591–607. doi: 10.1093/ajcn/47.4.591. [DOI] [PubMed] [Google Scholar]
  18. Fukagawa N. K., Minaker K. L., Rowe J. W., Goodman M. N., Matthews D. E., Bier D. M., Young V. R. Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men. J Clin Invest. 1985 Dec;76(6):2306–2311. doi: 10.1172/JCI112240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Guler H. P., Schmid C., Zapf J., Froesch E. R. Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2868–2872. doi: 10.1073/pnas.86.8.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Hussain M. A., Schmitz O., Mengel A., Keller A., Christiansen J. S., Zapf J., Froesch E. R. Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans. J Clin Invest. 1993 Nov;92(5):2249–2256. doi: 10.1172/JCI116828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Karlander S., Vranić M., Efendić S. Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance. Diabetologia. 1986 Nov;29(11):778–783. doi: 10.1007/BF00873216. [DOI] [PubMed] [Google Scholar]
  23. Kupfer S. R., Underwood L. E., Baxter R. C., Clemmons D. R. Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously. J Clin Invest. 1993 Feb;91(2):391–396. doi: 10.1172/JCI116212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laron Z., Anin S., Klipper-Aurbach Y., Klinger B. Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. Lancet. 1992 May 23;339(8804):1258–1261. doi: 10.1016/0140-6736(92)91594-x. [DOI] [PubMed] [Google Scholar]
  25. Leahy J. L., Vandekerkhove K. M. Insulin-like growth factor-I at physiological concentrations is a potent inhibitor of insulin secretion. Endocrinology. 1990 Mar;126(3):1593–1598. doi: 10.1210/endo-126-3-1593. [DOI] [PubMed] [Google Scholar]
  26. Møller N., Jørgensen J. O., Schmitz O., Møller J., Christiansen J., Alberti K. G., Orskov H. Effects of a growth hormone pulse on total and forearm substrate fluxes in humans. Am J Physiol. 1990 Jan;258(1 Pt 1):E86–E91. doi: 10.1152/ajpendo.1990.258.1.E86. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Rizza R. A., Mandarino L. J., Gerich J. E. Effects of growth hormone on insulin action in man. Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes. 1982 Aug;31(8 Pt 1):663–669. doi: 10.2337/diab.31.8.663. [DOI] [PubMed] [Google Scholar]
  29. Rossetti L., Smith D., Shulman G. I., Papachristou D., DeFronzo R. A. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest. 1987 May;79(5):1510–1515. doi: 10.1172/JCI112981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. SALMON W. D., Jr, DAUGHADAY W. H. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. 1957 Jun;49(6):825–836. [PubMed] [Google Scholar]
  31. Salomon F., Cuneo R. C., Hesp R., Sönksen P. H. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989 Dec 28;321(26):1797–1803. doi: 10.1056/NEJM198912283212605. [DOI] [PubMed] [Google Scholar]
  32. Scheiwiller E., Guler H. P., Merryweather J., Scandella C., Maerki W., Zapf J., Froesch E. R. Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Nature. 1986 Sep 11;323(6084):169–171. doi: 10.1038/323169a0. [DOI] [PubMed] [Google Scholar]
  33. Schwander J. C., Hauri C., Zapf J., Froesch E. R. Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology. 1983 Jul;113(1):297–305. doi: 10.1210/endo-113-1-297. [DOI] [PubMed] [Google Scholar]
  34. Segal K. R., Van Loan M., Fitzgerald P. I., Hodgdon J. A., Van Itallie T. B. Lean body mass estimation by bioelectrical impedance analysis: a four-site cross-validation study. Am J Clin Nutr. 1988 Jan;47(1):7–14. doi: 10.1093/ajcn/47.1.7. [DOI] [PubMed] [Google Scholar]
  35. Sherwin R. S., Schulman G. A., Hendler R., Walesky M., Belous A., Tamborlane W. Effect of growth hormone on oral glucose tolerance and circulating metabolic fuels in man. Diabetologia. 1983 Mar;24(3):155–161. doi: 10.1007/BF00250154. [DOI] [PubMed] [Google Scholar]
  36. Zapf J., Schoenle E., Waldvogel M., Sand I., Froesch E. R. Effect of trypsin treatment of rat adipocytes on biological effects and binding of insulin and insulin-like growth factors: further evidence for the action of insulin-like growth factors through the insulin receptor. Eur J Biochem. 1981 Jan;113(3):605–609. doi: 10.1111/j.1432-1033.1981.tb05105.x. [DOI] [PubMed] [Google Scholar]
  37. Zenobi P. D., Graf S., Ursprung H., Froesch E. R. Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. J Clin Invest. 1992 Jun;89(6):1908–1913. doi: 10.1172/JCI115796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Buul-Offers S., Ueda I., Van den Brande J. L. Biosynthetic somatomedin C (SM-C/IGF-I) increases the length and weight of Snell dwarf mice. Pediatr Res. 1986 Sep;20(9):825–827. doi: 10.1203/00006450-198609000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES