Relationship of energy production to gluconeogenesis in renal cortical tubules

Abstract

Isolated tubules prepared by collagenase treatment of rat renal cortex retained their ultrastructural integrity and responded to added lactate and succinate with an increase in gluconeogenesis and respiration. Inhibition of the mitochondrial respiratory chain with rotenone, or energy conservation sites with oligomycin caused a marked reduction in respiration and ATP content thereby completely inhibiting net gluconeogenesis. Dissociation of gluconeogenesis from respiration was accomplished with quinolinic acid and hydrazine, inhibitors of gluconeogenesis. At 5 times 10(-3) M quinolinic acid, gluconeogenesis from succinate was inhibited approximately 50% and from lactate nearly 100%. This concentration of quinolinic acid did not affect oxygen uptake or the ATP content of tubules in the presence or absence of substrate. Hydrazine at 10(-3) M resulted in approximately 75% inhibition of glucose formation from succinate and complete inhibition from lactate without interfering with respiration or ATP content. The increased mitochondrial energy generation, as manifested by accelerated respiration was independent of gluconeogenesis. The unchanging cell ATP concentration with a higher respiratory rate upon addition of exogenous substrate bespeaks increased ATP turnover. ATP utilization for the substrate-induced enhancement of gluconeogenesis could not account for the increment in ATP hydrolysis.

Diadenosine polyphosphate-stimulated gluconeogenesis in isolated rat proximal tubules

“…Table 1 shows the effect of a range of adenine-containing effectors on the gluconeogenic activity of isolated rat proximal tubules incubated in the presence of either 10 mM lactate or 10 mM glutamine (gluconeogenic precursors). The substrate-supported glucose-production rates, which were maintained over a 1 h incubation period, were similar to those observed previously by ourselves [20] and other workers [28], thereby confirming the metabolic viability of the tubule preparations. Exogenous adenosine promoted an approx.…”