Summary
In order to explain the abnormalities of glucose metabolism previously observed in patients with blood ammonia elevation, the effect of a transitory hyperammonemia on I. V. glucose tolerance was investigated in rats. An I. V. glucose tolerance test was performed in 3 groups of 15 rats 60 min after the beginning of a 95 min infusion of either a 2 ml isotonic NaCl solution (control group) or ammonium acetate solutions at low (0.50 μmol/kg/min. NH4+) or high doses (1.70 μmol/kg/min NH4+). The “high” NH4+infusion produced an increase of blood ammonia to levels near 1000 μg/100 ml, a significant decrease in the K coefficient for glucose disappearance (2.53 × 10−2±0.20 compared to 4.92 × 10−2±0.13 in control group) and a suppression of the radioimmunological plasma insulin (I.R.I.) response to glucose. With the “low” NH4 + infusion the hyperammonemia was less pronounced (200–300 μg/100 ml), but the decrease in K(3.02 × 10−2±0.15) and in the first phase of I.R.I, release remained significant. The decrease in glucose disappearance rate could be accounted for by the proportional decrease in insulin secretion. Thus glucose intolerance induced by ammonium acetate infusions may be due to a direct effect of NH4 + on the pancreas. These abnormalities in glucose metabolism depend on the quantity of infused ammonium.
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Albano, O., Francavilla, A.: Intracellular potassium concentration during ammonia intoxication. Gastroenteroly 61, 893–897 (1971)
Alleyne, G. A. O., Fraser, H. S., Besterman, H. S.: Some effect of metabolic acidosis on carbohydrate metabolism in the rat. Clin. Sci. 39, 375–382 (1970)
Amatuzio, D. S., Rames, F. D., Nesbitt, S.: The practical application of the rapid intravenous glucose tolerance test in various states affecting glucose metabolism. J. Lab. clin. Med. 48, 714–720 (1956)
Bessman, S. P., Bessman, A. N.: Cerebral and peripheral uptake of ammonia in liver disease with a hypothesis of mechanism of hepatic coma. J. clin. Invest 34, 622–628 (1955)
Blakely, R. L., Hinds, J. A., Kunze, H. E., Webb, E. C., Zerner, B.: Jackbean urease (E.C.3.5.1.5), demonstration of carbamyl transfer reaction and inhibition by hydroxamic acid. Biochemistry 8, 1991–1999 (1969)
Brown, H., O'Hara, E., Brown, N. E., Covelli V. H., Konda, D., Mc Dermott, Jr. W. V.: Relation of blood glucose to blood ammonia and urea cycle enzymes. J. Amer. med. Ass. 199, 641–646 (1967)
Christophe, J.: Détermination d'un coefficient d'assimilation glucidique chez le rat normal. Etude de l'influence de la dose de glucose sur l'assimilation. C. R. Soc. Biol. (Paris) 148, 1886–1889 (1954)
Clifford, A. J., Prior, R. L., Visek, W. J.: Concentrations of metabolic intermediates in blood and liver of rats acutely intoxicated with ammonia (abstract). Fed. Proc. 28, 301 (1969)
Conard, V., Rasio, E., Franckson, J. R. M: Physiological interpretation of glucose tolerance test. In: Pfeiffer, E.F.: Handbook of diabetes mellitus. (ed. J.F. Lehmann) München 2, 947–976 (1971)
Conn, H. O., Elkington, S. G.: Lack of correlation between blood glucose and ammonia concentrations. Amer. J. med. Sci. 257, 132–139 (1969)
Dawson, A. M., De Groote, J., Rosenthal, W. S., Sherlock, S.: Blood pyruvic-acid and alpha-ketoglutaric acid levels in liver disease and hepatic coma. Lancet 1957 I, 392–396
Fazekas, J. F., Ticktin, H. E., Ehrmantraut, W. R., Alman, R. W.: Cerebral metabolism in hepatic insufficiency. Amer. J. Med. 21, 843–849 (1956)
Feldman, J. M., Lebowitz, H. E.: Ammonium ion, modulator of insulin secretion. Amer. J. Physiol. 221, 1027–1032 (1971)
Grodsky, G. M., Benett, L. L.: Cation requirements for insulin secretion in the isolated perfused pancreas. Diabetes 15, 910–913 (1966)
Hales, C. N., Randle, P. J.: Immunoassay of insulin with insulin antibody precipitate. Biochem. J. 88, 137–151 (1963)
Hales, C. N., Milner, R. D. G.: The role of sodium and potassium in insulin secretion from rabbit pancreas. J. Physiol. (Lond.) 194, 725–743 (1968)
Hawkins, R. A., Miller, A. L., Nielsen, R. C., Veech, R. L.: The acute action of ammonia on rat brain metabolism in vivo. Biochem. J. 134, 1001–1008 (1973)
Hoffmann, W. S.: Rapid photoelectric method for determination of glucose in blood and urine. J. Biol. Biochem. 120, 51–55 (1937)
Howell, S. L., Taylor, K. W.: Potassium ions and the secretion of insulin by islet of Langerhans incubated in vitro. Biochem. J. 108, 17–24 (1968)
Imler, M., Frick, A., Stahl, A., Peter, B., Stahl, J.: Dosage de l'ammoniémie en discontinu et en continu par une technique de dialyse automatique. Clin. chim. Acta 37, 245–261 (1972)
Mackler, B., Lichtenstein, H., Guest, M.: Effects of ammonium chloride acidosis on glucose tolerance in dogs. Amer. J. Physiol. 168, 126–130 (1952)
Maiolo, A. T., Bianchi Porro, G., Galli, C., Sessa, M., Polli, E. E.: Brain energy metabolism in hepatic coma. Exp. Biol. Med. 4, 52–70 (1971)
Muntz, J. A., Hurwitz, J.: Effect of potassium and ammonium ions upon glycolysis catalyzed by an extract of rat brain. Arch. Biochem. Biophys. 32, 124–136 (1951)
Porte, D. Jr.: A receptor mechanism for the inhibition of insulin release by epinephrine in man. J. clin. Invest. 46, 86–94 (1967)
Prior, R. L., Clifford, A. J., Gibson, G. E., Visek, W. J.: Effect of insulin on glucose metabolism in hyperammonemic rats. Amer. J. Physiol. 221, 432–436 (1971)
Prior, R. L., Visek, W. J.: Effects of urea hydrolysis on tissue metabolite concentrations in rats. Amer. J. Physiol. 223, 1143–1149 (1972)
Roberts, K. E., Thompson, F. G. III, Popell, J. W., Vanamee, P.: Respiratory alkalosis accompanying ammonium toxicity. J. appl. Physiol. 9, 367–370 (1956)
Rodbard, D., Cooper, J. A.: A model for prediction of confidence limits in radio-immunoassays and competitive protein binding assays. In: In vitro procedures with radioisotopes in medicine, 1 vol., p. 659 Vienna: Int. Atomic energy agency Edit. 1970
Schenker, S., Mc Candless, D. V., Brophy, E., Lewis, M. S.: Studies on the intracerebral toxicity of ammonia. J. clin. Invest. 46, 838–848 (1967)
Schlienger, J. L., Imler, M., Stahl, J.: Etude de la tolérance glucosée au cours du coma hépatique. Path, et Biol. 22, 125–130 (1974)
Schlienger, J. L., Imler, M., Stahl, J.: Diminution de la tolérance glucosée chez l'homme sous l'effet de la perfusion de sels d'ammonium. Path, et Biol. 22, 465–470 (1974)
Schlienger, J. L., Imler, M., Stahl, J.: Diminution de la tolérance glucosée et de l'insulinosécrétion après perfusion de sels d'ammonium chez l'homme normal et chez des malades atteints de stéatose hépatique ou de cirrhose. Biol. et Gastroentérologie 7, 101–110 (1974)
Seltzer, H. S., Allen, E. W., Herron, A. L., Brennan, M. T.: Insulin secretion in response to glycemic stimulus. Relation of delayed release to carbohydrate intolerance in mild diabetes mellitus. J. clin. Invest 46, 323–335 (1967)
Sy, B. G., Duner, G., Steigmann, F., Dubin, A.: The effect of glucose infusion on ammonia metabolism in liver failure. Amer. J. med. Sci. 256, 91–96 (1968)
Summerskill, W. H. J., Wolfe, S. J., Davidson, C. S.: The metabolism of ammonia and alphaketoacids in liver disease and hepatic coma. J. clin. Invest 36, 361–372 (1957)
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Schlienger, J.L., Imler, M. & Stahl, J. Diabetogenic effect and inhibition of insulin secretion induced in normal rats by ammonium infusions. Diabetologia 11, 439–443 (1975). https://doi.org/10.1007/BF00429913
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DOI: https://doi.org/10.1007/BF00429913