Diabetologia

, Volume 20, Issue 2, pp 123–128

Metabolic effects of acute and prolonged growth hormone excess in normal and insulin-deficient man

  • P. Metcalfe
  • D. G. Johnston
  • R. Nosadini
  • H. Ørksov
  • K. G. M. M. Alberti
Originals

Summary

The metabolic effects of acute (4 h) and prolonged (24 h) growth hormone excess at pathophysiological concentrations were studied by growth hormone administration to normal subjects with and without somatostatin induced insulin deficiency. Acute growth hormone excess produced mild hyperinsulinaemia, but blood glucose concentrations were unaltered whereas chronic growth hormone excess caused a small (0.5 mmol/l) but significant rise in overnight-fasting blood glucose concentration together with a similar rise in fasting insulin levels (Mean ± SEM 9 ± 1 v 4 ± 1 mU/l, p<0.01). When insulin secretion was suppressed by somatostatin, a hyperglycaemic effect of acute growth hormone excess was unmasked, and the hyperglycaemic effect of chronic growth hormone excess was exaggerated. Acute growth hormone administration without somatostatin had a mild ketogenic action despite stimulated insulin secretion but no change in plasma non-esterified fatty acid or blood glycerol levels was observed. Somatostatin magnified the ketogenic effect of acute growth hormone excess, and unmasked a lipolytic action. Prolonged growth hormone excess had a lipolytic action that was increased by somatostatin, although the ketogenic effect of growth hormone was only seen during somatostatin induced insulin deficiency. The acute hyperglycaemic, lipolytic and ketogenic actions of growth hormone in normal subjects are limited by a compensatory rise in insulin secretion although with chronic exposure hyperglycaemic and lipolytic effects are seen. In insulin-deficient states, however, elevated growth hormone levels could be important in promoting hyperglycaemia and hyperketonaemia.

Key words

Growth hormone insulin insulin deficiency glucagon blood glucose ketone bodies ketogenesis lipolysis non-esterified fatty acids 

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References

  1. 1.
    Johansen K, Hansen AP (1969) High 24 hour levels of serum growth hormone in juvenile diabetics. Br Med J: 356–357Google Scholar
  2. 2.
    Hansen AP, Johansen K (1970) Diurnal pattern of blood glucose, serum FFA, insulin, glucagon and growth hormone in normals and juvenile diabetics. Diabetologia 6: 27–33Google Scholar
  3. 3.
    Hansen AP (1971) Normalisation of growth hormone hyper-response to exercise in juvenile diabetics after normalisation of blood sugar. J Clin Invest 50: 1806–1811Google Scholar
  4. 4.
    Merimee TJ, Fitzgerald CR, Gold LA, McCourt JP (1979) Characteristics of growth hormone secretion in clinically stable diabetes. Diabetes 28: 308–312Google Scholar
  5. 5.
    Young FG (1937) Permanent experimental diabetes produced by pituitary (anterior lobe) injections. Lancet II: 372–374Google Scholar
  6. 6.
    Houssay BA, Anderson E (1949) Diabetogenic action of purified anterior pituitary hormones. Endocrinology 45: 627–631Google Scholar
  7. 7.
    Ikkos D, Luft R, Gemzell C, Almquist S (1962) Effect of human growth hormone on glucose tolerance and some intermediary metabolites in man. Acta Endocrinol (Kbh) 39: 547–566Google Scholar
  8. 8.
    Ikkos D, Luft R (1962) Effect of short-term administration of large doses of human growth hormone on carbohydrate metabolism in adult, non-diabetic, hypophysectomised women; studies with 14C-labelled glucose. Acta Endocrinol (Kbh) 39: 567–583Google Scholar
  9. 9.
    Weil R (1965) Pituitary growth hormone and intermediary metabolism. Acta Endocrinol [Suppl 98] (Kbh) 49: 5–92Google Scholar
  10. 10.
    Luft R, Ikkos D (1958) Effect of growth hormone in hypophysectomised diabetic subjects. Lancet I: 721–722Google Scholar
  11. 11.
    Gerich JE, Lorenzi M, Bier DM, Tsalikian E, Schneider V, Karam JH, Forsham PH (1976) Effects of physiological levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. J Clin Invest 57: 875–884Google Scholar
  12. 12.
    Lloyd B, Burrin J, Smythe P, Alberti KGMM (1978) Simple automated enzymatic fluorimetric assays for blood glucose, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate. Clin Chem 24: 1724–1729Google Scholar
  13. 13.
    Price CP, Lloyd B, Alberti KGMM (1977) A kinetic spectrophotometric assay for rapid determination of acetoacetate in blood. Clin Chem 23: 1893–1897Google Scholar
  14. 14.
    Ho RT, Meng HC (1969) A simple and ultrasensitive method for determination of FFA by radiochemical assay. Anal Biochem 31: 425–436Google Scholar
  15. 15.
    Postle A, Goodland FC (1978) A comparison of three automated methods of serum triglyceride analysis. Ann Clin Biochem 15: 18–24Google Scholar
  16. 16.
    Boden G, Soeldner JS (1967) A sensitive double antibody radioimmuoassay for human growth hormone (HGH). Levels of HGH following rapid tolbutamide infusion. Diabetologia 3: 413–421Google Scholar
  17. 17.
    Soeldner J, Slone D (1965) Critical variables in the radioimmunoassay of serum insulin using the double antibody technique. Diabetes 14: 771–779Google Scholar
  18. 18.
    Alberti KGMM, Christensen NJ, Iversen J, Ørskov H (1975) The role of glucagon and other hormones in the development of diabetic ketoacidosis. Lancet I: 1307–1311Google Scholar
  19. 19.
    Baum CK, Tudor R, Landon J (1974) A simple competitive protein binding assay for plasma cortisol. Clin Chim Acta 55: 147–154Google Scholar
  20. 20.
    Chernick SS, Clark CM Jr, Gardiner RJ, Scow RO (1972) Role of lipolytic and glucocorticoid hormones in the development of diabetic ketosis. Diabetes 21: 946–954Google Scholar
  21. 21.
    Batstone GF, Alberti KGMM, Hinks L (1976) Metabolic studies in subjects following thermal injury: intermediate metabolites, hormones and tissue oxygenation. Burns 2: 207–225Google Scholar
  22. 22.
    Roos, R, Fevold HR, Gemzell CA (1963) Preparations of human growth hormone by gel filtration. Biochim Biophys Acta 74: 525–531Google Scholar
  23. 23.
    Holmstrom B, Fholenhag K (1975) Characterisation of human growth hormone preparations used for the treatment of pituitary dwarfism: a comparison of concurrently used batches. J Clin Endocrinol Metab 40: 856–862Google Scholar
  24. 24.
    Houssay BA, Biasotti A (1930) La diabetes pancreatica de los perros —hipofiseoprivos. Rev Soc Argent Biol 6: 251–258Google Scholar
  25. 25.
    Hierler KL, Rabinowitz D (1963) Roles of insulin and growth hormone based on studies of forearm metabolism in man. Medicine (Baltimore) 42: 385–402Google Scholar
  26. 26.
    Luft R (1969) The effects of moderate and high doses of human growth hormone on the insulin response to glucose infusion in prediabetic subjects. Horm Metab Res 1: 111–118Google Scholar
  27. 27.
    Merimee TJ (1967) Influence of growth hormone on insulin secretion. Studies of growth hormone deficient subjects. Diabetes 16: 478–482Google Scholar
  28. 28.
    Adamson U, Wahren J, Cerasi E (1977) Influence of growth hormone on splanchnic glucose production in man. Acta Endocrinol (Kbh) 86: 803–812Google Scholar
  29. 29.
    Lazarus S, Volk B (1962) In: The pancreas in human and experimental diabetes. Grune & Stratton, New YorkGoogle Scholar
  30. 30.
    Merimee TJ, Felig P, Marliss E, Fineberg SE, Cahill GF Jr (1971) Glucose and lipid homeostasis in the absence of human hormone. J Clin Invest 50: 574–582Google Scholar
  31. 31.
    Sirek A, Vranic M, Sirek Ou, Vigas M, Policova Z (1979) Effect of growth hormone on acute glucagon and insulin release. Am J Physiol 6: 107–112Google Scholar
  32. 32.
    Caldwell AB, Fain JN (1970) Inhibition by cycloheximide and dactinomycin of the activation of lipolysis due to growth hormone in white fat cells. Horm Metab Res 2: 3–5Google Scholar
  33. 33.
    Goodman HM, Schwartz J (1974) Growth hormone and lipid metabolism. In: Handbook of physiology, Section 7: Endocrinology 4. American Physiological Society, Washington DC, p 211–231Google Scholar
  34. 34.
    Nestel PH, White HM (1967) Relationship between FFA flux and TFGA influx in plasma before and during the infusions of insulin. Metabolism 16: 1123–1132Google Scholar
  35. 35.
    Fain JN (1968) Effect of dibutyryl-3′,5′-AMP, theophylline and norepinephrine on the lipolytic action of growth hormone and glucocorticoids in white fat cells. Endocrinology 82: 825–830Google Scholar
  36. 36.
    Penhos JC, Wu CH, Lemberg A, Daunas J, Brodoff B, Levine R (1966) The effect of growth hormone on the metabolism of lipids and on urea formation by the perfused rat liver. Metabolism 15: 1109–1119Google Scholar
  37. 37.
    Schade DS, Eaton RP, Peake GT (1978) The regulation of plasma ketone body concentration by counter-regulatory hormones in man. Diabetes 27: 916–924Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • P. Metcalfe
    • 1
  • D. G. Johnston
    • 2
  • R. Nosadini
    • 3
  • H. Ørksov
    • 4
  • K. G. M. M. Alberti
    • 3
  1. 1.Southampton University Medical SchoolSouthampton
  2. 2.Department of MedicineRoyal Victoria InfirmaryNewcastle upon TyneEngland
  3. 3.Departments of Clinical Biochemistry and Metabolic MedicineRoyal Victoria InfirmaryNewcastle upon TyneEngland
  4. 4.Afdeling MKommunehospitaletAarhusDenmark

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