Skip to main content
Log in

Effects of recombinant human insulin-like growth factor I and insulin on counterregulation during acute plasma glucose decrements in normal and Type 2 (non-insulin-dependent) diabetic subjects

  • Originals
  • Published:
Diabetologia Aims and scope Submit manuscript

Summary

Insulin-like growth factor I (65 μg/kg) or insulin (0.1 IU/kg) were injected i.v. on two separate occasions in random order in normal and in Type 2 (non-insulin-dependent) diabetic subjects. Insulin-like growth factor I and insulin injection resulted in identical decrements of plasma glucose concentrations after 30 min but in delayed recovery after insulin-like growth factor I as compared to insulin in both groups (p<0.05 insulin-like growth factor I vs insulin). Counterregulatory increases in plasma glucagon, adrenaline, cortisol and growth hormone concentrations after hypoglycaemia (1.9±0.2 mmol/l) in normal subjects were blunted after insulin-like growth factor I administration compared to insulin (p<0.05). Plasma glucose in Type 2 diabetic subjects did not reach hypoglycaemic levels but the acute glucose decrease to 4.5±0.8 mmol/l was associated with significantly lower responses of plasma glucagon and adrenaline but higher cortisol levels after insulin-like growth factor I compared to insulin (p<0.003). Plasma concentrations of non-esterified fatty acids and leucine decreased similarly after insulin-like growth factor I and insulin in both groups. The present results demonstrate that insulin-like growth factor I is capable of mimicking the acute effects of insulin on metabolic substrates (plasma glucose, non-esterified fatty acids, leucine). The decreases of plasma glucose were similar after both peptides in normal and in diabetic subjects who were presumably insulin resistant. Counterregulatory hormone responses to plasma glucose decrements differed, however, between insulin-like growth factor I and insulin and in the diabetic and the control subjects. After insulin-like growth factor I the increases in adrenaline, cortisol, growth hormone and glucagon were blunted in normal subjects despite slightly lower plasma glucose concentrations.

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.

Similar content being viewed by others

References

  1. Moxley RT, Arner P, Moss A et al. (1990) Acute effects of insulin-like growth factor I and insulin on glucose metabolism in vivo. Am J Physiol 59: 561–567

    Google Scholar 

  2. Rossetti L, Frontoni S, Dimarchi R, DeFronzo RA, Giaccari A (1991) Metabolic effects of IGF-I in diabetic rats. Diabetes 40: 444–448

    CAS  PubMed  Google Scholar 

  3. Jacob R, Barrett E, Plewe G, Fagin KD, Sherwin RS (1989) Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. J Clin Invest 83: 1717–1723

    CAS  PubMed  Google Scholar 

  4. Boulware SD, Tamborlane WV, Matthews LS, Sherwin RS (1992) Diverse effects of insulin-like growth factor 1 on glucose, lipid, and amino acid metabolism. Am J Physiol 262: E130-E133

    CAS  PubMed  Google Scholar 

  5. Turkalj I, Keller U, Ninnis R, Vosmeer S, Stauffacher W (1992) Effects of increasing doses of recombinant human insulin-like growth factor 1 on glucose, lipid and leucine metabolism in man. J Clin Endocr Metab 75: 1186–1191

    Article  CAS  PubMed  Google Scholar 

  6. Zenobi PD, Graf S, Ursprung H, Froesch ER (1992) Effects of insulin-like growth factor I on glucose tolerance, insulin levels and insulin secretion. J Clin Invest 89: 1908–1913

    CAS  PubMed  Google Scholar 

  7. Laager R, Ninnis R, Vosmeer S, Dembinsky K, Keller U (1992) Comparison of the metabolic effects of rh-insulin-like growth factor-1 (IGF-1) and of insulin in man. Diabetologia 35 [Suppl 1]: A 65 (Abstract)

    Google Scholar 

  8. Jacob JJ, Sherwin RS, Bowen L et al. (1991) Metabolic effects of IGF-I and insulin in spontaneously diabetic BB/w rats. Am J Physiol 260:E262-E268

    CAS  PubMed  Google Scholar 

  9. Guler H, Zapf J, Froesch ER (1987) Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med 317: 137–140

    CAS  PubMed  Google Scholar 

  10. Holst JJ, Aasted B (1974) Production and evaluation of glucagon antibodies for radioimmunoassay. Acta Endocrinol 77: 715–726

    CAS  PubMed  Google Scholar 

  11. Da Prada M, Zürcher G (1976) Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci 19: 1161–1174

    PubMed  Google Scholar 

  12. Girard J, Erb T, Pampalone A, Eberle AN, Baumann JB (1987) Growth hormone in urine: development of an ultrasensitive assay applicable to plasma and urine. Horm Res 28: 71–80

    CAS  PubMed  Google Scholar 

  13. Zapf J, Walter H, Froesch ER (1981) Radioimmunological determination of insulin-like growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 68: 1321–1330

    CAS  PubMed  Google Scholar 

  14. Herbert V, Kam-Seng L, Gottlieb CW, Bleicher SJ (1965) Coated charcoal immunoassay of insulin. J Clin Endocr 25: 1375–1384

    CAS  PubMed  Google Scholar 

  15. Miles J, Glasscock R, Aikens J, Gerich J, Haymond M (1983) A microfluorometric method for the determination of free fatty acids in plasma. J Lipid Res 24: 96–99

    CAS  PubMed  Google Scholar 

  16. Schwenk WF, Berg PF, Beaufrère B, Miles JM, Haymond MW (1984) Use of T-butyldimethylsilylation in the gas chromatographic-mass spectrometric analysis of physiologic compounds found in plasma using electron-impact ionization. Anal Biochem 141: 101–109

    CAS  PubMed  Google Scholar 

  17. Moller DE, Flier JS (1991) Insulin resistance: mechanisms, syndromes and implications. New Engl J Med 325: 938–943

    CAS  PubMed  Google Scholar 

  18. Bodkin NL, Sportsman R, DiMarchi RD, Hansen BC (1991) Insulin-like growth factor-1 in non-insulin dependent diabetic monkeys: basal plasma concentrations and metabolic effects of exogenously administered biosynthetic hormone. Metabolism 40: 1131–1137

    Article  CAS  PubMed  Google Scholar 

  19. Jacob R, Sherwin S, Greenawalt K, Shulman GI (1992) Simultaneous insulin-like growth factor I and insulin resistance in obese Zucker rats. Diabetes 41: 691–697

    CAS  PubMed  Google Scholar 

  20. Quin JD, Miles Fisher B, Paterson RK (1990) Acute responses to recombinant insulin-like growth factor I in a patient with Mendenhall's syndrome. New Engl J Med 323: 1425–1426

    CAS  PubMed  Google Scholar 

  21. Schoenle EJ, Zenobi PD, Torresani T et al. (1991) Recombinant human insulin-like growth factor I (rhIGF 1) reduces hyperglycaemia in patients with extreme insulin resistance. Diabetologia 34: 675–679

    Article  CAS  PubMed  Google Scholar 

  22. Usala AL, Madigan T, Burguera B et al. (1992) Brief report: treatment of insulin resistant diabetic ketoacidosis with insulinlike growth factor I in an adolescent with insulin-dependent diabetes. New Engl J Med 327: 853–857

    CAS  PubMed  Google Scholar 

  23. Liu D, Moberg E, Kollind M, Lins PE (1991) A high concentration of circulating insulin suppresses the glucagon response to hypoglycemia in normal man. J Clin Endocr Metab 73: 1123–1128

    CAS  PubMed  Google Scholar 

  24. Diamond MP, Hallarman L, Starick-Zych K et al. (1991) Suppression of counterregulatory hormone response to hypoglycemia by insulin per se. J Clin Endocr Metab 72: 1388–1390

    CAS  PubMed  Google Scholar 

  25. Mauras N, Horber FF, Haymond MW (1992) Low dose recombinant human insulin-like growth factor-I fails to affect protein anabolism but inhibits islet cell secretion in humans. J Clin Endocrinol Metab 75: 1192–1197

    Article  CAS  PubMed  Google Scholar 

  26. Gerich J, Davis J, Lorenzi M et al. (1979) Hormonal mechanisms of recovery from insulin-induced hypoglycemia in man. Am J Physiol 236:E380-E385

    CAS  PubMed  Google Scholar 

  27. De Feo P, Perriello G, Torlone E et al. (1989) Contribution of cortisol to glucose counterregulation in humans. Am J Physiol 257:E35-E42

    PubMed  Google Scholar 

  28. Kerr D, Tamborlane W, Frances R, Sherwin R (1993) Effect of Insulin-like growth factor 1 on the response to and recognition of hypoglycemia in humans. J Clin Invest 91: 141–147

    CAS  PubMed  Google Scholar 

  29. De Fronzo RA, Hendler R, Christensen N (1980) Stimulation of counterregulatory hormonal responses in diabetic man by a fall in glucose concentration. Diabetes 29: 125–131

    Google Scholar 

  30. Guler HP, Zapf J, Schmid C, Froesch ER (1989) Insulin-like growth factor I and II in healthy man. Estimation of half lives and production rates. Acta Endocrinol 121: 753–758

    CAS  PubMed  Google Scholar 

  31. Zapf J, Hauri C, Waldvogel M, Froesch ER (1986) Acute metabolic effects and half-lives of intravenously administered insulin-like growth factors I and II in normal and hypophysectomized rats. J Clin Invest 77: 1768–1775

    CAS  PubMed  Google Scholar 

  32. Zapf J, Schmid C, Guler HP et al. (1990) Regulation of binding proteins for insulin-like growth factors (IGF-1) in humans. J Clin Invest 86: 952–961

    CAS  PubMed  Google Scholar 

  33. Guler HP, Schmid C, Zapf J, Froesch E (1989) Effects of recombinant insulin-like growth factor-I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci USA 86: 2868–2872

    CAS  PubMed  Google Scholar 

  34. Bolinder J, Lindblad A, Engfeldt P, Arner P (1987) Studies of acute effects of insulin-like growth factors I and II in human fat cells. J Clin Endocrinol Metab 65: 732–737

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laager, R., Keller, U. Effects of recombinant human insulin-like growth factor I and insulin on counterregulation during acute plasma glucose decrements in normal and Type 2 (non-insulin-dependent) diabetic subjects. Diabetologia 36, 966–971 (1993). https://doi.org/10.1007/BF02374481

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02374481

Key words

Navigation