Control of glycolysis and gluconeogenesis in rat kidney cortex slices

Abstract

1. Glucose uptake or glucose formation has been studied in kidney cortex slices to investigate metabolic control of phosphofructokinase and fructose-diphosphatase activities. 2. Glucose uptake is increased and glucose formation is decreased by anoxia, cyanide or an uncoupling agent. Under these conditions the intracellular concentrations of glucose 6-phosphate and ATP decreased whereas that of fructose diphosphate either increased or remained constant, and the concentrations of AMP and ADP increased. 3. Glucose uptake was decreased, and glucose formation from glycerol or dihydroxyacetone was increased, by the presence of ketone bodies or fatty acids, or after starvation of the donor animal. Under these conditions, the concentrations of glucose 6-phosphate and citrate were increased, whereas those of fructose diphosphate and the adenine nucleotides were unchanged (see also Newsholme & Underwood, 1966). 4. It is concluded that anoxia and cell poisons increase glucose uptake and decrease gluconeogenesis by stimulating phosphofructokinase and inhibiting fructose diphosphatase, whereas ketone bodies, fatty acids or starvation increase gluconeogenesis and decrease glucose uptake through the citrate inhibition of phosphofructokinase.

The fuel of respiration of rat kidney cortex

“…Kidney-cortex slices of rats from three different dietary regimes were used. There was no significant effect of the high-carbohydrate diet on glucose uptake, but starvation for 48hr., in accordance with the findings of Underwood & Newsholme (1967), decreased the rate of glucose uptake by more than 50%. The rates of gas exchange were not significantly affected by the diets, although the respiratory quotient was slightly lower after starvation.…”

“…It is already known that the utilization of glucose by kidney-cortex slices is decreased on addition of palmitate or butyrate to the medium (Underwood & Newsholme, 1967), and that glucose, in contrast, has no effect on the formation of 14CO2 from labelled palmitate (Allen, Friedmann & Weinhouse, 1955). These observations indicate that fatty acids are a preferred fuel of respiration.…”

The effect of ketone bodies on renal ammoniogenesis

“…It is well-known that ketone bodies can be used as preferential respiratory fuel in the renal cortex where they are oxidized to acetyl Co-A (24,25,(29)(30)(31)(32)(33). The latter is coupled with oxaloacetate to form citrate under the catalytic activity of citrate synthetase and is thus incorporated in the tricarboxylic acid cycle (Fig.…”

Fuel selection by the kidney: adaptation to starvation

“…Although Elhamri et al (1993) could not demonstrate a statistically significant change in renal glucose handling during starvation, there was a tendency for glucose removal to decrease in their study. This may be due to (1) a decrease in glucose utilization in distal segments of the nephron resulting from an intrinsic decrease in the ability to metabolize and oxidize glucose (Underwood & Newsholme, 1967;Weidemann & Krebs, 1969;Hems & Gaja, 1972) and/or the increased availability and metabolism of ketone bodies and fatty acids (Underwood & Newsholme, 1967;Weidemann & Krebs, 1969) and (2) a starvation-induced stimulation of gluconeogenesis from lactate (Krebs et al 1963(Krebs et al , 1965(Krebs et al , 1966Janssens et al 1980), glutamine (Iynedjian & Peters, 1974;Bennett et al 1975), and glycerol (Krebs et al 1963;Underwood & Newsholme, 1967). In the proximal tubule, the increased conversion of lactate into glucose at the expense of lactate oxidation during starvation may result from the sparing effect of fatty acids and ketone bodies (Krebs et al 1965(Krebs et al , 1966 and from the stimulation of pyruvate carboxylase by an elevated cellular acetyl-CoA level (Krebs et al 1965).…”

“…Given that glycerokinase, the enzyme initiating glycerol metabolism and forming 3-glycerophosphate, has a significant activity exclusively in the rat proximal tubule (Burch et al 1982), the glycerol taken up across both the basolateral and apical membranes of the proximal tubular cells (Elhamri et al 1993) can be either incorporated into triacylglycerols whose synthesis occurs in these cells or converted into glucose or CO2 (Krebs et al 1963;Underwood & Newsholme, 1967). Although the supply of glycerol to the kidney did not change during starvation, the significant increase in glycerol utilization observed across the basolateral membrane of the proximal tubule (Elhamri et al 1993) does not necessarily mean that glycerol provided more energy (if any) to the proximal tubule because the renal cortex of starved rats stores more triacylglycerols (Hohenegger & Schuh, 1980; and probably forms more glucose from glycerol as a result of the increased activity of fructose bisphosphatase and glucose-6-phosphatase (Burch et al 19786).…”