Journal of Endocrinological Investigation

, Volume 10, Issue 6, pp 569–574 | Cite as

In vivo insulin antagonism but evanescent in vitro tissue effect in rats with growth hormone-secreting tumors

  • Mayer B. Davidson
  • D. C. Shen
  • N. Venkatesan
  • G. Sladen


Rats bearing mammosomatotropic tumors have raised insulin but lowered glucose concentrations. To determine if growth hormone (GH) secreted by these tumors causes insulin antagonism, pancreatic suppression tests utilizing infusions (per kg per min) of glucose (8 mg), insulin (200 ng) and somatostatin (1.4 μg) for 130 min were performed. Although the steady state plasma glucose and insulin levels (mean of 90, 100, 110, 120 and 130 min samples) were similar in 8 control and 13 tumor-bearing rats, the decrease from the already depressed basal glucose concentration (mmoles/l±SE) in the tumor animals was less than in the controls (0.90 ± 0.30 vs. 2.56 ± 0.040, p < 0.005). Since the interpretation of these results was not entirely clear, glucose and insulin-glucose tolerance tests were performed. The glucose disappearance rates (%/min ± SE) in the glucose tolerance test were lower in 17 tumor rats (2.00 ± 0.13) compared to 17 control animals (2.51 ± 0.22). This difference just missed statistical significance (t = 2.00, value of 2.04 necessary for p = 0.05). The decrease occurred in the presence of increased insulin (nmoles/l ×16 min) levels (4.29 ± 0.38 vs. 2.58 ± 0.29, p < 0.005) suggesting insulin antagonism. The glucose disappearance rates (%/min ± SE) in the insulin-glucose tolerance test were less in 12 tumor-bearing rats compared to 11 control animals (2.80 ± 0.29 vs. 4.12 ± 0.35, p < 0.02). Thus, these GH-secreting tumors cause insulin antagonism in vivo. Freshly isolated hepatocytes from these tumor-bearing animals manifest decreased insulin binding and action (Diabetologia 25: 60, 1983). In the present study, however, insulin binding and action (net glucose-C14 incorporation into glycogen) were normal after the hepatocytes were cultured for two days. This suggests that the changes induced by GH in vivo that lead to insulin antagonism are short-lived.


Growth hormone GH3 cells insulin antagonism insulin resistance 


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  1. 1.
    Davidson M.B., Melmed S. Hepatocyte insulin binding and action in rats with sommatomammotrophic tumours. Diabetologia 25: 60, 1983.PubMedCrossRefGoogle Scholar
  2. 2.
    Schwartz J. Enhanced sensitivity to insulin in rats treated with antibodies to rat growth hormone. Endocrinology 107: 877, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Gause I., Eden S., Jansson J-O., Isaksson O. Effects of in vivo administration of antiserum to rat growth hormone on body growth and insulin responsiveness in adipose tissue. Endocrinology 112: 1559, 1983.PubMedCrossRefGoogle Scholar
  4. 4.
    Martin J.M., Akerblom H.K., Garay G. Insulin secretion in rats with elevated levels of circulating growth hormone due to MtT–W15 tumor. Diabetes) 17: 661, 1968.Google Scholar
  5. 5.
    Garay G.L., Akerblom H.K., Martin J.M. Experimental hypersomatotropism: serum growth hormone and insulin, and pituitary and pancreatic changes in MtT–W15 tumor-bearing rats before and after tumor removal. Horm. Metab. Res. 3: 82, 1971.PubMedCrossRefGoogle Scholar
  6. 6.
    Akerblom H.K., Martin J.M., Garay G.L., Moscarello M. Experimental hypersomatotropism. II. Metabolic effects in rats bearing the MtT–W15 tumor. Horm. Metab. Res. 4: 15, 1972.PubMedCrossRefGoogle Scholar
  7. 7.
    Mahler R.J., Szabo O. The acute synergistic activity of growth hormone. II. Reversal of chronic growth hormone effect by Actinomycin D. Horm. Metab. Res. 1: 65, 1969.PubMedCrossRefGoogle Scholar
  8. 8.
    Tashjian A.H. Jr., Yasumura Y., Levine L., Sato G.H., Parker M.L. Establishment of clonal strains of rat pituitary tumor cells that secrete growth hormone. Endocrinology 82: 342, 1968.PubMedCrossRefGoogle Scholar
  9. 9.
    Melmed S. Insulin suppresses growth hormone secretion by rat pituitary cells. J. Clin. Invest. 73: 1425, 1984.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Zavaroni I., Sander S., Scott S., Reaven G.M. Effect of fructose feeding on insulin secretion and insulin action in the rat. Metabolism 29: 970, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Davidson M.B. Insulin resistance of late pregnancy does not include the liver. Metabolism 33: 532, 1984.PubMedCrossRefGoogle Scholar
  12. 12.
    Levy J., Gavin J.R. III., Fausto A., Gingerich R.L., Avioli L.V. Impaired insulin action in rats with non-insulin-dependent diabetes. Diabetes 33: 901, 1984.PubMedCrossRefGoogle Scholar
  13. 13.
    Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248, 1976.PubMedCrossRefGoogle Scholar
  14. 14.
    Bergmeyer H.U. Methods of enzymatic analysis. Academic Press, New York, 1974, vol. 3, p. 1196.Google Scholar
  15. 15.
    Catt K., Tregear G.W. Solid-phase radioimmunoassay in antibody-coated tubes. Science 158: 1570, 1967.PubMedCrossRefGoogle Scholar
  16. 16.
    Worcester J. The statistical method. N. Engl. J. Med. 274: 27, 1966.PubMedCrossRefGoogle Scholar
  17. 17.
    Dall’Aglio E., Chang F., Chang H., Wright D., Reaven G.M. Effect of exercise training and sucrose feeding on insulin-stimulated glucose uptake in rats with streptozotocin-induced insulin-deficient diabetes. Diabetes 32: 165, 1983.PubMedCrossRefGoogle Scholar
  18. 18.
    Landgraf R., Landraf-Leurs M.M.C., Weissmann A., Horl R., von Werder K., Scriba P.C. Prolactin: a diabetogenic hormone. Diabetologia 13: 99, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    Gustafson A.B., Banasiak M.F., Kalkhoff R.K., Hagen T.C., Kim H-J. Correlation of hyperprolactinemia with altered plasma insulin and glucagon: similarity to effect of late human pregnancy. J. Clin. Endocrinol. Metab. 51: 242, 1980.PubMedCrossRefGoogle Scholar
  20. 20.
    Katz E.J., Donald R.A., Beaven D.W., Espiner E.A. Lack of effect of hyperprolactinemia on glucose disposal and insulin secretion in patients with prolactinomas. Horm. Metab. Res. 13: 667, 1981.PubMedCrossRefGoogle Scholar
  21. 21.
    Rojdmark S., Lamminpaa K. Does acute endogenous hyperprolactinemia affect intravenous glucose tolerance in humans? Metabolism 33: 567, 1980.CrossRefGoogle Scholar
  22. 22.
    Scobie I.N., Kesson C.M., Ratcliffe J.G., MacCuish A.C. The effects of prolonged bromocriptine administration on PRL secretion GH and glycaemic control in stable insulin-dependent diabetes mellitus. Clin. Endocrinol. (Oxf.) 18: 179, 1983.CrossRefGoogle Scholar
  23. 23.
    Rathgeb I., Winkler B., Steele R., Altszuler N. Effect of ovine prolactin administration on glucose metabolism and plasma insulin levels in the dog. Endocrinology 88: 718, 1971.PubMedCrossRefGoogle Scholar
  24. 24.
    Renauld A., Sverdlik R.C., Andrade L.L. The effect of chronic prolactin administration upon the blood sugar, insulin and free fatty acid response to a glucose load in the dog. Acta Diabetol. Lat. 10: 1286, 1973.PubMedCrossRefGoogle Scholar
  25. 25.
    Manns J.G., Boda J.M. Effects of ovine growth hormone and prolactin on blood glucose, serum insulin, plasma nonesterified fatty acids and amino nitrogen in sheep. Endocrinology 76: 1109, 1965.PubMedCrossRefGoogle Scholar
  26. 26.
    Adler R.A., Sokol H.W. Glucose tolerance in rats with elevated circulating prolactin levels. Horm. Metab. Res. 14: 307, 1982.PubMedCrossRefGoogle Scholar
  27. 27.
    Davidson M.B. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr. Rev. 8: 115, 1987.PubMedCrossRefGoogle Scholar
  28. 28.
    Bates R.W., Scow R.O., Lacy P.E. Induction of permanent diabetes in rats by pituitary hormones from a transplantable mammotrophic tumor. Concomitant changes in organ weights and the effect of adrenalectomy. Endocrinology 78: 826, 1966.PubMedCrossRefGoogle Scholar
  29. 29.
    Venkatesan N., Davidson M.B. Dissociation of insulin binding from receptor kinase activity in the liver of rats chronically exposed to high growth hormone levels. Clin. Res. 35: 195, 1987.Google Scholar
  30. 30.
    Melmed S., Carlson H.E., Briggs J., Hershman J. Cell culture alters the hormonal response of rat pituitary tumors to dynamic stimulation. Endocrinology 107: 789, 1980.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1987

Authors and Affiliations

  • Mayer B. Davidson
    • 1
    • 2
  • D. C. Shen
    • 1
  • N. Venkatesan
    • 1
  • G. Sladen
    • 1
  1. 1.Department of MedicineCedars-Sinai Medical Center-UCLALos AngelesUSA
  2. 2.Division of Endocrinology, Room 1735Cedars-Sinai Medical CenterLos AngelesUSA

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