Advertisement

Diabetologia

, Volume 29, Issue 12, pp 882–887 | Cite as

Stimulation of 2-deoxyglucose uptake in rat adipocytes by a human growth hormone fragment (hGH 4-15)

  • F. M. Ng
  • J. A. Harcourt
Article

Summary

The in vivo and in vitro effects of a hypoglycaemic fragment of human growth hormone containing the sequence H2N-Ile-Pro- Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala-Met-Leu-COOH (hGH 4–15) on 2-deoxy-[1-14C]-D-glucose uptake in adipocytes were studied. The isolated cells from rats after a single intravenous injection of hGH 4–15 (1 mg/kg) significantly increased uptake of 2-deoxyglucose (p < 0.005). Adipocytes from untreated rats pre-incubated with the hGH fragment (10 μg/ml) at 37°C for 30 min also clearly showed an elevated uptake of 2-deoxyglucose in the absence and the presence of exogenous insulin. The effect of hGH 4–15 was concentration-dependent, steadily increasing with the maximum effect at 10 μg/ml. The present findings suggest that the enhancement of glucose transport in target tissues may be a major contributing factor to the hypoglycaemic action of the amino-terminal fragments of human growth hormone.

Key words

Human growth hormone synthetic fragment 4–15 glucose transport rat adipocytes 

References

  1. 1.
    Millman AE, Russell JA (1950) Some effects of purified pituitary growth hormone on carbohydrate metabolism in rat. Endocrinology 47: 114–128Google Scholar
  2. 2.
    Mahler RJ, Szabo O (1969) Early insulin synergistic activity of growth hormone. Diabetes 18: 550–555Google Scholar
  3. 3.
    Baumann G, MacCart JG, Amburn K (1983) The molecular nature of circulating growth hormone in normal and acromegalic man: evidence for a principal and minor monomeric forms. J Clin Endocrinol Metab 56: 946–952Google Scholar
  4. 4.
    Baumann G, Abramson EC (1983) Urinary growth hormone in man: evidence for multiple molecular forms. J Clin Endocrinol Metab 56: 305–311Google Scholar
  5. 5.
    Paladini AC, Pena C, Poskus E (1983) Molecular biology of growth hormone. CRC Crit Rev Biochem 15: 25–56Google Scholar
  6. 6.
    Chawla RK, Parks JS, Rudman D (1984) Structural variants of human growth hormone. Ann Rev Med 34: 519–547Google Scholar
  7. 7.
    Ng FM, Bornstein J, Welker C, Zimmet PZ, Taft P (1974) Insulinpotentiating action of synthetic peptide relating to the amino terminal sequence of human growth hormone. Diabetes 23: 943–949Google Scholar
  8. 8.
    Ng FM, Bornstein J (1979) Insulin potentiating action of a synthetic amino-terminal fragment of human growth hormone (hGH 1–15) in streptozotocin-diabetic rats. Diabetes 28: 1126–1130Google Scholar
  9. 9.
    Singh RNP, Seavey BK, Lewis LJ, Lewis UJ (1983) Human growth hormone peptide 1-43: Isolation from pituitary glands. J Protein Chem 2: 425–436Google Scholar
  10. 10.
    Lewis UJ (1984) Variants of growth hormone and prolactin and their post-translational modification. Ann Rev Physiol 46: 33–42Google Scholar
  11. 11.
    Ng FM, Bornstein J (1982) Comparison of hypoglycaemic responses to human growth hormone and the synthetic 4-15 fragment between 16–18 day old and 45–50 day old rats. Diabetologia 23: 534–538Google Scholar
  12. 12.
    Ng FM, Larner J (1976) Actions of insulin-potentiating peptides on glycogen synthesis. Diabetes 25: 413–419Google Scholar
  13. 13.
    Sims P, Ng FM, Bornstein J (1980) Modulation of adipocytes insulin receptors by a human growth hormone fragment. Biochem Int 1: 120–125Google Scholar
  14. 14.
    Ng FM, Bornstein J, Pullin CO, Bromely JO, Macaulay SL (1980) The minimal amino acid sequence of the insulin-potentiating fragment of human growth hormone. Diabetes 29: 782–787Google Scholar
  15. 15.
    Pullin CO, Harcourt JA, Ng FM, Bornstein J (1981) The insulinpotentiating action of human growth hormone-synthesis and activity of N-terminal fragments. Int J Peptide Protein Res 18: 318–323Google Scholar
  16. 16.
    Ng FM, Henderson T, Bromley JO, Bornstein J (1983) Modulation of hepatic insulin receptors by a human growth hormone fragment (hGH 6–13). Mol Cellul Endocrinol 30: 63–71Google Scholar
  17. 17.
    Armstrong J, Bornstein J, Bromley JO, Macaulay SL, Ng FM (1983) Parallel insulin-like action of human growth hormone and its part sequence hGH 7–13. Acta Endocrinologia 103: 479–486Google Scholar
  18. 18.
    Karnieli E, Hissin PJ, Simpson IA, Safaris LB, Cushman SW (1981) A possible mechanism of insulin resistance in the rat adipose cell in streptozotocin-induced diabetes mellitus. J Clin Invest 68: 811–814Google Scholar
  19. 19.
    Olefsky JM (1978) Mechanisms of the ability of insulin to activate the glucose-transport system in rat adipocytes. Biochem J 172: 137–145Google Scholar
  20. 20.
    Martin BR, Denton RM, Pask HT, Randle PJ (1972) Mechanism regulating adipose tissue pyruvate dehydrogenase. Biochem J 129: 763–773Google Scholar
  21. 21.
    Lawrence JC, Guinovart JJ, Lamer J (1977) Activation of rat adipocyte glycogen synthase by insulin. J Biol Chem 252: 444–450Google Scholar
  22. 22.
    Rodbell M (1964) Metabolism of isolated fat cells. I. Effect of hormones on glucose metabolism and lipolysis. J Biol Chem 239: 375–380Google Scholar
  23. 23.
    Foley JE, Laursen AL, Sonne O, Gliemann J (1980) Insulin binding and hexose transport in rat adipocytes. Diabetologia 19: 234–241Google Scholar
  24. 24.
    Folch J, Lees M, Stanley GHS (1956) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509Google Scholar
  25. 25.
    Jungas RL (1964) Fatty acid synthesis in adipose tissue incubated in tritated water. J Biol Chem 239: 675–681Google Scholar
  26. 26.
    Ma GYW, Macaulay SL, Maggs JA, Armstrong JMcD, Bornstein J (1982) The mechanism of the hypoglycaemic action of synthetic peptides related to the C-terminal sequence of human growth hormone. Biochim Biophys Acta 716: 400–409Google Scholar
  27. 27.
    Newman JD, Armstrong JMcD, Bornstein J (1978) Effect of part sequence of human growth hormone on in vivo hepatic glycogen metabolism in the rat. Biochem Biophys Acta 544: 234–240Google Scholar
  28. 28.
    Kobayashi M, Olefsky JM (1978) Effect of experimental hyperinsulinemia on insulin binding and glucose transport in isolated rat adipocytes. Am J Physiol 235: E53-E62Google Scholar
  29. 29.
    Gliemann J, Osterlind K, Vinten J, Gammeltoft S (1972) A procedure for measurement of distribution space in isolated fat cells. Biochem Biophys Acta 286: 1–9Google Scholar
  30. 30.
    May JM, Mikulecky DC (1983) Glucose utilization in rat adipocytes. J Biochem Chem 258: 4771–4777Google Scholar
  31. 31.
    Foley JE, Cushman SW, Salans LB (1980) Intracellular glucose concentration in small and large rat adipose cells. Am J Physiol 238: E180-E185Google Scholar
  32. 32.
    Gliemann J, Rees WD, Foley JA (1984) The rate of labelled glucose molecules in the rat adipocyte dependence on glucose concentration. Biochim Biophys Acta 804: 68–76Google Scholar
  33. 33.
    Czech MP (1980) Insulin action and the regulation of hexose transport. Diabetes 29: 399–409Google Scholar
  34. 34.
    Tsuda M, Taketomi S, Iwatsuka H (1980) Selective inhibition by neuraminidase of insulin/action on hexose metabolism of mouse adipocytes. Am J Physiol 239: E186-E191Google Scholar
  35. 35.
    Cuatrecasas P, Illiano G (1971) Membrane sialic acid and the mechanism of insulin action in adipose tissue cells. Effect of digestion with neuraminidase. J Biol Chem 246: 4938–4946Google Scholar
  36. 36.
    Tsuda M, Taketomi S, Iwatsuka H (1980) Selective inhibition by neuraminidase of insulin action on hexose metabolism of mouse adipocytes. Am J Physiol 239: E186-E191Google Scholar
  37. 37.
    Blackard WG, Small E, Ludeman C (1980) Inhibition of insulin binding by concanavalin A. Metabolism 29: 691–697Google Scholar
  38. 38.
    Ludvigsen C, Jarett L (1982) Similarities between insulin, hydrogen peroxide, concanavalin A, and anti-insulin receptor antibody stimulated glucose transport: Increase in the number of transport site. Metabolism 31: 284–287Google Scholar
  39. 39.
    Tannenbaum J, Tannenbaum SW, Godman GC (1977) The binding sites of cytochalasin D. J Cell Physiol 91: 239–248Google Scholar
  40. 40.
    Jarett L, Smith RM (1979) Effect of cytochalasin B and D on groups of insulin receptors and on insulin action in rat adipocytes. J Clin Invest 63: 571–579Google Scholar
  41. 41.
    Kono T, Barham FW (1971) Insulin-like effects of trypsin on fat cells. J Biol Chem 246: 6204–6209Google Scholar
  42. 42.
    Jarett L, Smith RM (1979) Effect of cytochalasin B and D on groups of insulin receptors and on insulin action in rat adipocytes. J Clin Invest 63: 571–579Google Scholar
  43. 43.
    Maloff BL, Levine JH, Lockwood DH (1980) Direct effects of growth hormone on insulin action in rat adipose tissue maintained in vitro. Endocrinology 107: 538–544Google Scholar
  44. 44.
    Goodman HM, Coiro V (1981) Induction of sensitivity to the insulin-like action of growth hormone in normal rat adipose tissue. Endocrinology 108: 413–119Google Scholar
  45. 45.
    Eden S, Schwartz J, Kostyo JL (1982) Effects of preincubation on the ability of rat adipocytes to bind and respond to growth hormone. Endocrinology 111: 1505–1512Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • F. M. Ng
    • 1
  • J. A. Harcourt
    • 1
  1. 1.Department of Biochemistry, Faculty of MedicineMonash UniversityClaytonAustralia

Personalised recommendations