Different Actions of Glucagon and Fatty Acids on Gluconeogenesis from Lactate in the Perfused Rat Liver

Abstract

The effect of glucagon on gluconeogenesis from lactate in the presence of high concentrations of albumin-bound fatty acids has been studied in the isolated perfused livers of starved rats. Simultaneously, ketone formation has been measured.

In the presence of either 1 mM oleic acid or 1.5 mM octanoate, basal gluconeogenesis was stimulated by the same degree (+75%). In contrast, ketone formation from octanoate exceeded that from oleic acid by about 100%. Thus, a rate of ketogenesis beyond that obtained with oleic acid was not accompanied by a further increase in glucose formation.

Simultaneous addition of glucagon with either oleic acid or octanoate resulted in the same additive stimulation of gluconeogenesis. This supports the view of different mechanisms of action of fatty acids and glucagon on gluconeogenesis.

Glucagon, in the presence of oleic acid, gave rise to an additive stimulation of ketogenesis, while, on the other hand, no further increase in ketogenesis was observed together with octanoate. This indicates a dissociation of the gluconeogenetic and ketogenetic action of glucagon.

Key words

Isolated Perfused Liver - Gluconeogenesis - Ketogenesis - Fatty Acids - Glucagon

1 * Present address: Medizinische Universitätsklinik, D 78 Freiburg, Hugstetter Str. (Germany)