Summary
The effect of physiological elevation of growth hormone levels on ketone body kinetics was determined using a 14C-ketone body tracer technique in normal and acutely insulin-deficient man. Changes of ketone body production and metabolic clearance rates during growth hormone infusion (plasma levels of approximately 25 μg/l) were measured during basal conditions and during heparin-induced elevation of non-esterified fatty acid levels. Growth hormone administration to six subjects fasted overnight resulted in an increase in ketone body production which exceeded that observed in nine control subjects (5.5±0.5 versus 3.1±0.1μmol·kg-1·min-1, p<0.025) after elevation of plasma non-esterified fatty acids. Growth hormone infusion increased glycerol and non-esterified fatty acid concentrations indicating enhanced lipolysis. During somatostatin-induced acute insulin deficiency (n=7), growth hormone enhanced the increase in total ketone body production observed in six subjects receiving somatostatin alone (8.4±0.8 versus 4.1±0.7μmol·kg-1·min-1, p<0.01). Total ketone body metabolic clearance decreased by 50% during somatostatin and remained uninfluenced by growth hormone. Non-esterified fatty acids and glycerol levels increased during somatostatin, and growth hormone failed to alter nonesterified fatty acid levels significantly. The results demonstrate a stimulatory effect of high physiological growth hormone levels on ketogenesis which is largely explained by an enhancement of lipolysis and thus increase in substrate supply for ketogenesis. Growth hormone administration during acute insulin deficiency enhanced ketogenesis in the absence of alterations in plasma non-esterified fatty acid levels, suggesting a direct hepatic ketogenic effect.
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Hansen AP (1970) Abnormal serum growth hormone response to exercise in juvenile diabetics. J Clin Invest 49: 1467–1478
Vigneri R, Squatrito S, Pezzino V, Filetti S, Branca S, Polosa P (1976) Growth hormone levels in diabetes. Correlation with the clinical control of the disease. Diabetes 25: 167–172
Alberti KGMM, Christensen NJ, Iversen J, Orskov H (1975) The role of glucagon and other hormones in the development of diabetic ketoacidosis. Lancet 1: 1307–1311
Popp DA, Shah SD, Cryer PE (1982) Role of epinephrine-mediated beta-adrenergic mechanisms in hypoglycemic glucose counterregulation and posthypoglycemic hyperglycemia in insulindependent diabetes mellitus. J Clin Invest 69: 315–326
Levy LJ, Duga J, Girgis M, Gordon EE (1973) Ketoacidosis associated with alcoholism in non-diabetic subjects. Ann Intern Med 78: 213–219
Best CH, Campbell J (1936) Anterior pituitary extracts and liver fat. J Physiol (London) 86: 190–203
Houssay BA, Anderson E (1949) Diabetogenic action of purified anterior pituitary hormones. Endocrinology 45: 627–631
Young PG (1937) Permanent experimental diabetes produced by pituitary (anterior lobe) injections. Lancet 2: 372–374
Luft R, Ikkos D (1958) Effect of growth hormone in hypophysectomised diabetic subjects. Lancet 1: 721–722
Raben NS, Hollenberg CH (1959) Effect of growth hormone on plasma fatty acids. J Clin Invest 38: 484–488
Felig P, Marliss EB, Cahill GF Jr. (1971) Metabolic response to human growth hormone during prolonged starvation. J Clin Invest 50: 411–421
Metcalfe P, Johnston DG, Nosadini R, Ørskov H, Alberti KGMM (1981) Metabolic effects of acute and prolonged growth hormone excess in normal and insulin-deficient man. Diabetologia 20: 123–128
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
Gerich J, Lorenzi M, Bier DM, Tsalikian E, Schneider V, Karam JH, Forsham PH (1976) Effects of physiologic levels of glucagon and growth hormone on human carbohydrate lipid metabolism. J Clin Invest 57: 875–884
Schade DS, Eaton PR, Peake GT (1978) The regulation of plasma ketone body concentration by counter-regulatory hormones in man. II. Effects of growth hormone in diabetic man. Diabetes 27: 916–924
Geigy Ltd, Basel (1960) Geigy Documenta. Scientific Tables, 6th ed.
Sonnenberg GE, Keller U (1982) Sampling of arterialized heatedhand venous blood as a noninvasive technique for the study of ketone body kinetics in man. Metabolism 1: 1–5
Keller U, Sonnenberg GE, Stauffacher W (1981) Validation of a tracer-technique to determine non-steady state ketone body turnover rates in man. Am J Physiol 240: E253-E260
Mayes PA, Felts JM (1967) Determination of 14C-labelled ketone bodies by liquid-scintillation counting. Biochem J 102: 230–235
Keller U, Cherrington AD, Liljenquist JE (1978) Ketone body turnover and hepatic ketone production in fasted and in diabetic dogs. Am J Physiol 235: E238-E247
Van Stekelenburg GJ, De Bruyn JW (1970) A simple gas Chromatographic determination of acetone and β-ketobutyric acid in blood serum by means of head space gas sampling. Clin Chim Acta 28: 233–237
Ho RJ (1970) Radiochemical assay of long-chain fatty acids using 63Ni as tracer. Analyt Biochem 36: 105–113
Heding LG (1972) Determination of total serum insulin in insulintreated diabetic patients. Diabetologia 8: 260–266
Girard J, Baumann JB, Stahl M, Nars PW, Bühler U, Wick H (1971) Experience with insulin-induced hypoglycemia as a provocative test for growth hormone and cortisol secretion in children. Hormones 2: 338–365
Aguilar-Parada E, Eisentraut AM, Unger RH (1969) Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci 257: 415–419
Holst JJ, Aasted B (1974) Production and evaluation of glucagon antibodies for radioimmunoassay. Acta Endocrinol 77: 715–726
Spitzer JJ, Nakamura H, Hori S, Gold M (1969) Hepatic and splanchnic uptake and oxidation of free fatty acids. Proc Soc Exp Biol Med 132: 281–286
Basso LV, Havel RJ (1970) Hepatic metabolism of free fatty acids in normal and diabetic dogs. J Clin Invest 49: 537–547
Lotspeich WD, Petersen VP (1954) Effect of anterior pituitary growth hormone on synthesis of acetoacetate by surviving slices of rat liver. Am J Physiol 176: 232–238
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. Metab Clin Exp 15: 1109–1119
Bennett LL, Kreiss RE, Hao Li CH, Evans HM (1948) Production of ketosis by the growth and adrenocorticotropic hormones. Am J Physiol 152: 210–215
Fineberg SE, Merimee TJ (1974) Acute metabolic effects of human growth hormone. Diabetes 23: 499–513
MacGorman LR, Rizza RA, Gerich JE (1981) Physiological concentrations of growth hormone exert insulin-like and insulin antagonistic effects on both hepatic and extrahepatic tissues in man. J Clin Endocrinol Metab 53: 556–559
Daughaday WH, Kipnis DM (1966) The growth promoting and anti-insulin actions of somatotropin. Rec Prog Horm Res 22: 49–93
Balasse EO, Havel RJ (1971) Evidence for an effect of insulin on the peripheral utilization of ketone bodies in dogs. J Clin Invest 50: 801–817
Cherrington AD, Caldwell MD, Dietz MR, Exton JH, Crofford OB (1977) The effect of somatostatin on glucose uptake and production by rat tissues in vitro. Diabetes 26: 740–748
Sonnenberg GE, Stauffacher W, Keller U (1982) Failure of glucagon to stimulate ketone body production during acute insulin deficiency or insulin replacement in man. Diabetologia 23: 94–100
Wright PD, Johnston IDA (1975) The effect of surgical operation on growth hormone levels in plasma. Surgery 77: 497–486
Hunter WM, Fonseka CC, Passmore R (1965) The role of growth hormone in the mobilization of fuel for muscular exercise. Q J Exp Physiol 50: 406–415
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Keller, U., Schnell, H., Girard, J. et al. 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 (1984). https://doi.org/10.1007/BF00281115
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DOI: https://doi.org/10.1007/BF00281115