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. 1992 Sep;216(3):280–290. doi: 10.1097/00000658-199209000-00007

Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients.

R F Wolf 1, D B Pearlstone 1, E Newman 1, M J Heslin 1, A Gonenne 1, M E Burt 1, M F Brennan 1
PMCID: PMC1242608  PMID: 1417177

Abstract

The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient.

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Selected References

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  1. Akaza H., Matsuki K., Matsushima H., Koiso K., Aso Y. Stimulatory effects of growth hormone on rat bladder carcinogenesis. Cancer. 1991 Dec 1;68(11):2418–2421. doi: 10.1002/1097-0142(19911201)68:11<2418::aid-cncr2820681115>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  2. Allsop J. R., Wolfe R. R., Burke J. F. Tracer priming the bicarbonate pool. J Appl Physiol Respir Environ Exerc Physiol. 1978 Jul;45(1):137–139. doi: 10.1152/jappl.1978.45.1.137. [DOI] [PubMed] [Google Scholar]
  3. Atherton N. D., Green A. HPLC measurement of phenylalanine in plasma. Clin Chem. 1988 Nov;34(11):2241–2244. [PubMed] [Google Scholar]
  4. BISHOP J. S., MARKS P. A. Studies on carbohydrate metabolism in patients with neoplastic disease. II. Response to insulin administration. J Clin Invest. 1959 Apr;38(4):668–672. doi: 10.1172/JCI103845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barrett E. J., Revkin J. H., Young L. H., Zaret B. L., Jacob R., Gelfand R. A. An isotopic method for measurement of muscle protein synthesis and degradation in vivo. Biochem J. 1987 Jul 1;245(1):223–228. doi: 10.1042/bj2450223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brennan M. F. Total parenteral nutrition in the cancer patient. N Engl J Med. 1981 Aug 13;305(7):375–382. doi: 10.1056/NEJM198108133050705. [DOI] [PubMed] [Google Scholar]
  7. Buse M. G., Reid S. S. Leucine. A possible regulator of protein turnover in muscle. J Clin Invest. 1975 Nov;56(5):1250–1261. doi: 10.1172/JCI108201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Castellino P., Luzi L., Simonson D. C., Haymond M., DeFronzo R. A. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest. 1987 Dec;80(6):1784–1793. doi: 10.1172/JCI113272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dewys W. D., Begg C., Lavin P. T., Band P. R., Bennett J. M., Bertino J. R., Cohen M. H., Douglass H. O., Jr, Engstrom P. F., Ezdinli E. Z. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980 Oct;69(4):491–497. doi: 10.1016/s0149-2918(05)80001-3. [DOI] [PubMed] [Google Scholar]
  10. Douglas R. G., Humberstone D. A., Haystead A., Shaw J. H. Metabolic effects of recombinant human growth hormone: isotopic studies in the postabsorptive state and during total parenteral nutrition. Br J Surg. 1990 Jul;77(7):785–790. doi: 10.1002/bjs.1800770722. [DOI] [PubMed] [Google Scholar]
  11. Dresler C. M., Jeevanandam M., Brennan M. F. Extremity blood flow in man: comparison between strain-gauge and capacitance plethysmography. Surgery. 1987 Jan;101(1):35–39. [PubMed] [Google Scholar]
  12. Durnin J. V., Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr. 1974 Jul;32(1):77–97. doi: 10.1079/bjn19740060. [DOI] [PubMed] [Google Scholar]
  13. Fryburg D. A., Gelfand R. A., Barrett E. J. Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans. Am J Physiol. 1991 Mar;260(3 Pt 1):E499–E504. doi: 10.1152/ajpendo.1991.260.3.E499. [DOI] [PubMed] [Google Scholar]
  14. Gore D. C., Honeycutt D., Jahoor F., Wolfe R. R., Herndon D. N. Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients. Arch Surg. 1991 Jan;126(1):38–43. doi: 10.1001/archsurg.1991.01410250042006. [DOI] [PubMed] [Google Scholar]
  15. Heymsfield S. B., McManus C. B. Tissue components of weight loss in cancer patients. A new method of study and preliminary observations. Cancer. 1985 Jan 1;55(1 Suppl):238–249. doi: 10.1002/1097-0142(19850101)55:1+<238::aid-cncr2820551306>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  16. Horber F. F., Haymond M. W. Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest. 1990 Jul;86(1):265–272. doi: 10.1172/JCI114694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jeevanandam M., Horowitz G. D., Lowry S. F., Brennan M. F. Cancer cachexia and protein metabolism. Lancet. 1984 Jun 30;1(8392):1423–1426. doi: 10.1016/s0140-6736(84)91929-9. [DOI] [PubMed] [Google Scholar]
  18. Jiang Z. M., He G. Z., Zhang S. Y., Wang X. R., Yang N. F., Zhu Y., Wilmore D. W. Low-dose growth hormone and hypocaloric nutrition attenuate the protein-catabolic response after major operation. Ann Surg. 1989 Oct;210(4):513–525. doi: 10.1097/00000658-198910000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klein S., Simes J., Blackburn G. L. Total parenteral nutrition and cancer clinical trials. Cancer. 1986 Sep 15;58(6):1378–1386. doi: 10.1002/1097-0142(19860915)58:6<1378::aid-cncr2820580635>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  20. Manson J. M., Smith R. J., Wilmore D. W. Growth hormone stimulates protein synthesis during hypocaloric parenteral nutrition. Role of hormonal-substrate environment. Ann Surg. 1988 Aug;208(2):136–142. doi: 10.1097/00000658-198808000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Manson J. M., Wilmore D. W. Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. Surgery. 1986 Aug;100(2):188–197. [PubMed] [Google Scholar]
  22. Marcus R., Butterfield G., Holloway L., Gilliland L., Baylink D. J., Hintz R. L., Sherman B. M. Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab. 1990 Feb;70(2):519–527. doi: 10.1210/jcem-70-2-519. [DOI] [PubMed] [Google Scholar]
  23. Ng E. H., Rock C. S., Lazarus D., Staiano-Coico L., Fischer E., Moldawer L. L., Lowry S. F. Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model. J Surg Res. 1991 Aug;51(2):99–105. doi: 10.1016/0022-4804(91)90077-y. [DOI] [PubMed] [Google Scholar]
  24. Nissen S., Van Huysen C., Haymond M. W. Measurement of plasma alpha-ketoisocaproate concentrations and specific radioactivity by high-performance liquid chromatography. Anal Biochem. 1981 Jan 15;110(2):389–392. doi: 10.1016/0003-2697(81)90208-6. [DOI] [PubMed] [Google Scholar]
  25. Pisters P. W., Cersosimo E., Rogatko A., Brennan M. F. Insulin action on glucose and branched-chain amino acid metabolism in cancer cachexia: differential effects of insulin. Surgery. 1992 Mar;111(3):301–310. [PubMed] [Google Scholar]
  26. Ponting G. A., Halliday D., Teale J. D., Sim A. J. Postoperative positive nitrogen balance with intravenous hyponutrition and growth hormone. Lancet. 1988 Feb 27;1(8583):438–440. doi: 10.1016/s0140-6736(88)91232-9. [DOI] [PubMed] [Google Scholar]
  27. Ponting G. A., Ward H. C., Halliday D., Sim A. J. Protein and energy metabolism with biosynthetic human growth hormone in patients on full intravenous nutritional support. JPEN J Parenter Enteral Nutr. 1990 Sep-Oct;14(5):437–441. doi: 10.1177/0148607190014005437. [DOI] [PubMed] [Google Scholar]
  28. ROE C. F., KINNEY J. M. The influence of human growth hormone on energy sources in convalescence. Surg Forum. 1962;13:369–371. [PubMed] [Google Scholar]
  29. Rudman D., Feller A. G., Nagraj H. S., Gergans G. A., Lalitha P. Y., Goldberg A. F., Schlenker R. A., Cohn L., Rudman I. W., Mattson D. E. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1–6. doi: 10.1056/NEJM199007053230101. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Schwenk W. F., Beaufrere B., Haymond M. W. Use of reciprocal pool specific activities to model leucine metabolism in humans. Am J Physiol. 1985 Dec;249(6 Pt 1):E646–E650. doi: 10.1152/ajpendo.1985.249.6.E646. [DOI] [PubMed] [Google Scholar]
  32. Shaw J. H., Humberstone D. A., Douglas R. G., Koea J. Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support. Surgery. 1991 Jan;109(1):37–50. [PubMed] [Google Scholar]
  33. Soroff H. S., Rozin R. R., Mooty J., Lister J., Raben M. S. Role of human growth hormone in the response to trauma. I. Metabolic effects following burns. Ann Surg. 1967 Nov;166(5):739–752. doi: 10.1097/00000658-196711000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Svaninger G., Isaksson O., Lundholm K. Growth hormone and experimental cancer cachexia. J Natl Cancer Inst. 1987 Dec;79(6):1359–1365. [PubMed] [Google Scholar]
  35. Torosian M. H., Donoway R. B. Growth hormone inhibits tumor metastasis. Cancer. 1991 May 1;67(9):2280–2283. doi: 10.1002/1097-0142(19910501)67:9<2280::aid-cncr2820670912>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  36. Wilmore D. W., Moylan J. A., Jr, Bristow B. F., Mason A. D., Jr, Pruitt B. A., Jr Anabolic effects of human growth hormone and high caloric feedings following thermal injury. Surg Gynecol Obstet. 1974 Jun;138(6):875–884. [PubMed] [Google Scholar]
  37. Younes R. N., Vydelingum N. A., Noguchi Y., Brennan M. F. Lipid kinetic alterations in tumor-bearing rats: reversal by tumor excision. J Surg Res. 1990 Apr;48(4):324–328. doi: 10.1016/0022-4804(90)90067-c. [DOI] [PubMed] [Google Scholar]
  38. Ziegler T. R., Young L. S., Manson J. M., Wilmore D. W. Metabolic effects of recombinant human growth hormone in patients receiving parenteral nutrition. Ann Surg. 1988 Jul;208(1):6–16. doi: 10.1097/00000658-198807000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]

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