RESUMO
The drug phenyl ethyl biguanide (PEBG) was used in vivo and in vitro to study further the relationship between renal gluconeogenesis and ammonia production in the rat. When PEBG was injected intraperitoneally into the rats, it caused a decrease in urinary ammonia in spite of a greater degree of systemic acidosis. PEBG injections also blocked the increase in glucose and ammonia production by renal cortical slices from rats which had been made acidotic by oral administration of ammonium chloride 2h previously. With increasing concentrations of PEBG in vitro, there was inhibition of gluconeogenesis and ammonia production from glutamine and glutamate as substrates. The two processes were equally inhibited when glutamate was used as substrate but with glutamine, gluconeogenesis was more inhiblted than ammonia production. The inhibition of renal gluconeogenesis by PEBG in vitro was similar when succinate, oxaloacetate, fructose, glutamine and glutamate were used as substrates. The results show that PEBG does not inhibit gluconeogenesis by blocking a specific site in the gluconeogenic pathway. In addition, further proof is provided of the physiological interrelationship of renal ammonia production and gluconeogenesis (Summary)
Assuntos
Ratos , 21003 , Técnicas In Vitro , Biguanidas/farmacocinética , Gluconeogênese , Amônia/metabolismo , Amônia/urina , Glutamatos , Glutamina , Córtex Renal/metabolismo , Glucose/metabolismo , Succinatos , Oxaloacetatos , FrutoseRESUMO
Metabolic acidosis was induced by feeding ammonium chloride to rats which were maintained on a carbohydrate diet for 48h. Fasting blood glucose was the same in acidotic and control animals, but there was an increase in liver glycogen in the former. Muscle glucogen was unchanged. In vitro glycogenesis was the same in liver slices from normal rats when incubated at a range of pH from 6.90 to 7.40. The peak blood glucose in response to intraperitoneal injections of glucagon was the same in control and acidotic rats. The rate of disappearence of glucose was slower in acidotic rats both after the glucagon induced hyperglycaemia and after intravenously injected glucose. Liver phosphorylase, total glycogen synthetase and the I form of this enzyme were unchanged in acidosis. The data are compatible with the hypothesis that in the acidotic rat there is a block in glycolysis-possibly at the phosphofructokinase step (Summary)