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Insulin-like growth factor-I in man enhances lipid mobilization and oxidation induced by a growth hormone pulse

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Summary

Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27±4 years, BMI 21.8±1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8 Μg · kg−1 · h−1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg−1 · day−1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p<0.02) and C-peptide levels by 78% (p<0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10±0.43 (saline) to 2.79±0.37 ml · 100ml−1 · min−1 (IGF-I) (p<0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9±7.4 ng/ml. GH did not influence circulating levels of total IGFI, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702±267 (saline) and 885±236 (IGF-I) to 963±215 (saline) (p<0.05) and 1815±586 Μmol/l (IGF-I) (p<0.02), respectively; after 5 h, 3-OH-butyrate rose from 242±234 (saline) and 340±280 (IGF-I) to 678±638 (saline) (p<0.02) and 1115±578 Μmol/l (IGF-I) (p<0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44±195 to 300±370 after 20 min (p<0.03) and to 287±91 nmol · 100 ml−1 · min−1after 120 min (p<0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.

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Abbreviations

AUC:

Area under the curve

C-peptide:

connecting peptide

EE:

energy expenditure

FFM:

fat-free mass

GH:

growth hormone

IGF-I:

insulin-like growth factor-I

NEFA:

non-esterified fatty acid

Ra:

rate of glucose appearance

Rd:

rate of glucose disposal

FGU:

forearm glucose uptake

CV:

coefficient of variation

References

  1. Takahashi Y, Kipnis DM, Daughaday WH (1968) Growth hormone secretion during sleep. J Clin Invest 47: 2079–2090

    Article  PubMed  CAS  Google Scholar 

  2. Finkelstein JW, Roffwarg HP, Boyar RM, Kream J, Helmann L (1972) Age-related changes in the twenty-four hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 36: 665–670

    Google Scholar 

  3. Schwander JC, Hauri C, Zapf J, Froesch ER (1983) Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology 113: 297–305

    PubMed  CAS  Google Scholar 

  4. Salmon WD, Daughaday WH (1957) A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vivo. J Lab Clin Med 49: 825–836

    PubMed  CAS  Google Scholar 

  5. Bar RS, Clemmons DR, Boes M, Busby WH, Booth BA, Dake BL (1990) Transcapillary permeability and distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart. Endocrinology 127: 1078–1086

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  8. Laager R, Ninnis R, Keller U (1993) Comparison of the effects of recombinant human insulin-like growth factor-I on glucose and leucine kinetics in humans. J Clin Invest 92: 1903–1909

    Article  PubMed  CAS  Google Scholar 

  9. Kupfer SR, Underwood LE, Baxter RC, Clemmons DR (1993) Enhancement of the anabolic effects of growth hormone and insulin-like growth factor-I by the use of both agents simultaneously. J Clin Invest 91: 391–397

    Article  PubMed  CAS  Google Scholar 

  10. Hussain MA, Schmitz O, Mengel A, Christiansen JS, Zapf J, Froesch ER (1994) Comparison of the effects of growth hormone and insulin-like growth factor-I on substrate oxidation and on insulin sensitivity in growth hormone deficient humans. J Clin Invest 94: 1126–1133

    Article  PubMed  CAS  Google Scholar 

  11. Guler HP, Schmid C, Zapf J, Froesch ER (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

    Article  PubMed  CAS  Google Scholar 

  12. Hussain MA, Schmitz O, Mengel A, Christiansen JS, Zapf J, Froesch ER (1993) Insulin-like growth factor-I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans. J Clin Invest 92: 2249–2256

    Article  PubMed  CAS  Google Scholar 

  13. Bratusch-Marrain PR, Smith D, De Fronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973–982

    PubMed  CAS  Google Scholar 

  14. Rizza R, Mandarino LW, Gerich JE (1982) Effects of growth hormone on insulin action in man. Mechanism of insulin resistance, impaired suppression of glucose utilization. Diabetes 31: 663–669

    Article  PubMed  CAS  Google Scholar 

  15. Sherwin RS, Schulman GA, Hendler R, Walesky M, Belous A, Tamborlane W (1983) Effect of growth hormone on oral glucose tolerance and circulating metabolic fuels in man. Diabetologia 24: 155–161

    Article  PubMed  CAS  Google Scholar 

  16. Salomon F, Cuneo RC, Hesp R, Sonksen P (1989) The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321: 1797–1803

    PubMed  CAS  Google Scholar 

  17. Möller N, Jörgensen JOL, Schmitz O et al. (1990) Effects of a growth hormone pulse on total and forearm substrate fluxes in humans. Am J Physiol 258:E86-E91

    PubMed  Google Scholar 

  18. Möller N, Butler PC, Antsiferov M, Alberti KGMM (1989) Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man. Diabetologia 32: 105–110

    Article  PubMed  Google Scholar 

  19. Coles DR, Cooper KE, Mottram RF, Occleshaw JV (1958) The source of blood samples withdrawn from deep forearm veins via catheters passed upstream from the median cubital vein. J Physiol Lond 142: 323–328

    PubMed  CAS  Google Scholar 

  20. Abumrad NN, Rabin ND, Diamond MP, Lacy WW (1981) Use of heated superficial hand veins as alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metab Clin Exp 30: 936–940

    PubMed  CAS  Google Scholar 

  21. Whitney RJ (1953) The measurement of volume changes in human limb. J Physiol 121: 1–27

    PubMed  CAS  Google Scholar 

  22. Segal KR, Van Loan RM, Fitzgerald PI, Hodgson JA, Van Italie TB (1988) Lean body mass estimation by bioelectrical impedance analysis: a four-site cross validation study. Am J Clin Nutr 47: 7–14

    PubMed  CAS  Google Scholar 

  23. Völund A, Brange J, Drejer K (1991) In vivo and in vitro potency of insulin analogues designed for clinical use. Diabet Med 8: 839–847

    PubMed  Google Scholar 

  24. Zapf J, Walter H, Froesch ER (1981) Radioimmunological determination of insulin-like growth factor-I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 86: 952–961

    Article  Google Scholar 

  25. Lloyd B, Burrin J, Smythe P, Alberti KGMM (1978) A simple automated fluorimetric assay for blood glucose, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate. Clin Chem 24: 1724–1729

    PubMed  CAS  Google Scholar 

  26. DeBodo R, Steele R, Altszuler N, Dunn A, Bishop J (1963) On the hormonal regulation of carbohydrate metabolism: studies with 14C glucose. Recent Prog Horm Res 19: 445–488

    PubMed  CAS  Google Scholar 

  27. Elia M, Livesey G (1988) Theory and validity of indirect calorimetry during net lipid synthesis. Am J Clin Nutr 47: 591–607

    PubMed  CAS  Google Scholar 

  28. Cooper KE, Edholm OG, Mottram RF (1955) The blood flow in skin and muscle of the human forearm. J Physiol Lond 128: 258–267

    PubMed  CAS  Google Scholar 

  29. Wilcoxon F (1945) Individual comparisons by ranking methods. Biomed Bull 1: 880–883

    Google Scholar 

  30. Tai MM (1994) A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care 2: 152–154

    Article  Google Scholar 

  31. Dietz J, Schwartz J (1991) Growth hormones alter lipolysis and hormone sensitive lipase activity in 3T3-F442A adipocytes. Met Clin Exp 40: 800–806

    CAS  Google Scholar 

  32. Metcalfe P, Johnston DG, Nosadini R, Orskov H, Alberti KGMM (1981) Metabolic effects of acute and prolonged growth hormone excess in normal and insulin-deficient man. Diabetologia 20: 123–128

    Article  PubMed  CAS  Google Scholar 

  33. Keller U, Schnell H, Girard J, Stauffacher W (1984) Effect of physiological elevation of plasma growth hormone levels on ketone body kinetics and lipolysis in normal and acutely insulin-deficient man. Diabetologia 26: 103–108

    Article  PubMed  CAS  Google Scholar 

  34. Press M (1988) Growth hormone and metabolism. Diabetes Metab Review 4: 391–414

    CAS  Google Scholar 

  35. Rosenthal MJ, Woodside WF (1988) Nocturnal regulation of free fatty acids in healthy young and elderly men. Metabolism 37: 645–648

    Article  PubMed  CAS  Google Scholar 

  36. Froesch ER, Hussain MA (1993) Therapeutic potential of rhIGF-I in diabetes and conditions of insulin resistance. J Int Med 234: 561–570

    CAS  Google Scholar 

  37. 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

    Article  PubMed  CAS  Google Scholar 

  38. Mauras N, Horber FF, Haymond MW (1992) Low dose recombinant 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  PubMed  CAS  Google Scholar 

  39. Rennert NJ, Caprio S, Sherwin RS (1993) Insulin-like growth factor I inhibits glucose-stimulated insulin secretion but does not impair glucose metabolism in normal humans. J Clin Endocrinol Metab 76: 804–806

    Article  PubMed  CAS  Google Scholar 

  40. Wildendorf KE (1972) Diurnal variations in the concentrations of blood acetate, 3-hydroxybutyrate and glucose in normal persons. Acta Med Scand 191: 303–306

    Google Scholar 

  41. Schade DS, Eaton RP, Peake GT (1978) The regulation of plasma ketone body concentration by counter-regulatory hormones in man. Diabetes 27: 916–924

    PubMed  CAS  Google Scholar 

  42. Gerich JE, Lorenzi M, Bier DM et al. (1976) Effects of physiological levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. J Clin Invest 57: 875–884

    Article  PubMed  CAS  Google Scholar 

  43. Jörgensen JOL, Möller J, Alberti KGMM et al. (1993) Marked effects of sustained low growth hormone levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects. J Clin Endocrinol Metab 6: 1589–1596

    Article  Google Scholar 

  44. Copeland KC, Nair KS (1994) Recombinant human insulin-like growth factor I increases forearm blood flow. J Clin Endocrinol Metab 79: 230–232

    Article  PubMed  CAS  Google Scholar 

  45. Hussain MA, Schmitz O, Christiansen JS, Zapf J, Froesch ER (1994) Insulin-like growth factor-I increases forearm blood flow at a non-hypoglycemic dose. 15th International Diabetes Federation Meeting, November 1994, Kobe, Japan (Abstract)

  46. Fukagawa NK, Minaker KL, Good WR et al. (1990) Acute effects of insulin-like growth factor I on leucine. Diabetes 38 [Suppl 1]:12A (Abstract)

    Google Scholar 

  47. Fryburg DA, Gelfand RA, Barrett EJ (1991) Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans. Am J Physiol 260:E499-E504

    PubMed  CAS  Google Scholar 

  48. Horber FF, Haymond MW (1990) Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest 86: 265–272

    Article  PubMed  CAS  Google Scholar 

  49. Copeland KC, Nair KS (1994) Acute growth hormone effects on amino acid and lipid metabolism. J Clin Endocrinol Metab 78: 1040–1047

    Article  PubMed  CAS  Google Scholar 

  50. Beaufrere B, Beylot M, Metz C, Ruitton A, Francois R, Riou JP, Mornex R (1988) Dawn phenomenon in type 1 (insulin-dependent) diabetic adolescents: influence of nocturnal growth hormone secretion. Diabetologia 31: 607–611

    Article  PubMed  CAS  Google Scholar 

  51. Edge JA, Matthews DR, Dunger DB (1990) The dawn phenomenon is related to overnight growth hormone release in adolescent diabetics. Clin Endocrinol 33: 729–733

    Article  CAS  Google Scholar 

  52. Edge JA, Dunger DB, Matthews DR, Gilbert JR, Smith CP (1990) Increased overnight growth hormone concentrations in diabetic compared with normal adolescent. J Clin Endocrinol Metab 71: 1356–1362

    Article  PubMed  CAS  Google Scholar 

  53. Cheetham TD, Clayton KL, Holly JM, Taylor AM, Connors M, Dunger DB (1994) In vivo use of recombinant human IGF-I: studies in type 1 diabetes. In: Baxter RC, Gluckman PD, Rosenfeld RG (eds) The insulin-like growth factors and their regulatory proteins. Elsevier Science B. V., Amsterdam, The Netherlands, pp 437–448

    Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital of Zürich, RÄmistrasse 100, CH-8091, Zürich, Switzerland

    T. L. Bianda, M. A. Hussain, A. Keller, Y. Glatz & E. R. Froesch

  2. Second University Clinic of Internal Medicine, Aarhus Kommunehospital, Aarhus, Denmark

    O. Schmitz & J. S. Christiansen

  3. Department of Medicine, The Royal Victoria Infirmary, Newcastle Upon Tyne, UK

    K. G. M. M. Alberti

Authors
  1. T. L. Bianda
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  2. M. A. Hussain
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  3. A. Keller
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  4. Y. Glatz
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  5. O. Schmitz
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  6. J. S. Christiansen
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  7. K. G. M. M. Alberti
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  8. E. R. Froesch
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Bianda, T.L., Hussain, M.A., Keller, A. et al. Insulin-like growth factor-I in man enhances lipid mobilization and oxidation induced by a growth hormone pulse. Diabetologia 39, 961–969 (1996). https://doi.org/10.1007/BF00403916

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  • DOI: https://doi.org/10.1007/BF00403916

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