RESUMO
2,5-Anhydro-D-mannitol inhibited glucose synthesis, increased the pyruvate/phosphoenolpyruvate ratio and altered adenine nucleotide concentrations in hepatocytes isolated from fasted rats. The accumulations of 2,5-anhydro-D-mannitol 1,6-diphosphate, an allosteric activator of pyruvate kinase, and of ADP in treated hepatocytes can account for the increase in pyruvate/phosphoenolpyruvate ratio and the inhibition of glucose synthesis from lactate.
Assuntos
Gluconeogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Manitol/análogos & derivados , Nucleotídeos de Adenina/metabolismo , Animais , Jejum , Técnicas In Vitro , Lactatos/metabolismo , Ácido Láctico , Fígado/metabolismo , Masculino , Manitol/farmacologia , Piruvato Quinase/metabolismo , Ratos , Ratos EndogâmicosRESUMO
2,5-Anhydro-D-mannitol, an analog of D-fructofuranose, inhibited basal and glucagon-stimulated glycogenolysis and glucose production in hepatocytes isolated from fed rats. Glucose formation from galactose was unaffected by the inhibitor. 2,5-Anhydro-D-mannitol-1-phosphate inhibits phosphorylase alpha with a Ki value of 2.4 mM. This same phosphorylated metabolite accumulates to the extent of 9.2 mumol/g wet wt in treated hepatocytes suggesting that phosphorolysis is the locus of the inhibition of glucose production from glycogen. Our results suggest that 2,5-anhydro-D-mannitol can be used to produce a model of hereditary fructose intolerance and that it merits further study as a hypoglycemic agent.
