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 rain infusion of either a 2 ml isotonic NaC1 solution (control group) or ammonium acetate solutions at low (0.50 gmol/kg/min. NI-I4+ ) or high doses (1.70 ~tmol/kg/min NH4+ ). The "high" NH4+ infusion produced an increase of blood ammonia to levels near 1000 ~tg/100 ml, a significant decrease in the K coefficient for glucose disappearance (2.53 x 10-24-0.20 compared to 4.92 x 10 -a 4-0.13 in control group) and a suppression of the radioimmunological plasma insulin (I. R. I.) response to glucose.With the "low" NH 4 -/-infusion the hyperammonemia was less pronounced (200-300 gg/100 ml), but the decrease in K(3.02 x 10 -2 4-0.15) 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 NI"I 4 "1-on the pancreas. These abnormalities in glucose metabolism depend on the quantity of infused ammonium.Key words: Rat, ammonium infusion, blood ammonia, glucose metabolism, plasma immunoreactive insulin.In 1955 Bessman et al [4] suggested that the neurotoxicity of hyperammonemia in porto-systemic encephalopathy results from a disturbance in cerebral glucose utilization. The observation, in hepatic coma, of a decrease in cerebral oxygen consumption [12,22] and an increase in some intermediates of glucose metabolism [11,35] supports this hypothesis. However the influence of variations in ammonium metabolism on the regulation of carbohydrate metabolism is still debated [10,34]. Recently, we noted that I. V. glucose tolerance was worse in cirrhotic patients with hepatic coma than in those without porto-systemic encephalopathy [30]. One factor which could explain this observation, was the increase in arterial blood ammonia which was consistently observed during hepatic coma. Thus we noted in both normal and cirrhotic subjects, infused with ammonium chloride or acetate, that a transitory elevation in arterial blood ammonia invariably brought about a very significant diminution in I. V. glucose tolerance [31] and an inhibition of the insulin secretion induced by the glucose load [32]. However, in these studies, we were unable to show any correlation between these anomalies and the blood ammonia levels. The aim of * Presented at the 9th Meeting of the European Association for the Study of the Liver. Hemsedal, Norway, september [6][7] 1974 the present study was to compare in normal rats the action of a moderate or gross hyperammonemia on glucose tolerance and insulin secretion.
Material and MethodsThree groups of 15 male Wistar rats, weighing 250-300 g and fasted for 20 hours, were used. Afte...