Substrate Uptake and Utilization by the Kidney of Fed and Starved Rats in vivo

Abstract

In order to obtain information (1) on the quantitative contribution of various circulating substrates to renal metabolism and (2) on the relative importance of net luminal and basolateral transport for substrate uptake, we have precisely quantified the renal blood flow, the urinary flow, and the rates of substrate handling by the kidney of anesthetized fed and 72-hour-starved rats. For this, the concentration of twelve metabolites were simultaneously measured in arterial and venous whole blood and plasma as well as in urine of each rat thanks to the use of microassays based on enzymatic cycling. In fed rats, the main potential energy sources were glucose and lactate followed by fatty acids, ketone bodies, citrate and glycerol. Starvation caused a large increase in renal uptake and metabolism of fatty acids, ketone bodies, glutamine and glycerol, and a large inhibition of lactate utilization. The net peritubular uptake of acetoacetate, citrate, glycerol and free fatty acids demonstrated in both nutritional states was increased by starvation only for glycerol and free fatty acids; net peritubular efflux of both β-hydroxybutyrate and ammonium ions was stimulated whereas that of glutamine was converted into net peritubular uptake by starvation.

Fuel selection by the kidney: adaptation to starvation

“…The observation that citrate was taken up across both the apical and basolateral membranes of renal cells (Elhamri et al 1993) is consistent with the existence of tricarboxylate carriers at both poles of the renal cells (Windus et al 1986;Burckhardt & Ullrich, 1989). Since virtually all the filtered citrate is reabsorbed in the proximal tubule (Simpson, 1983), and since reabsorption provided half the citrate metabolized by the kidney (Elhamri etal.…”

“…0 2 equivalents: 3 for lactate; 3.5 for glycerol, 4.0 for acetoacetate, 4.5 for glutamine, glutamate, P-hydroxybutyrate and citrate, 6 for glucose and 23 for FFA. Elhamri et al (1993) recognized that, given the small percentage of circulating glucose extracted by the kidney, their data on renal handling of this substance, like those of other authors, are not reliable. Thus, depending on whether the glucose uptake is included in the calculations (Table l), the sum of the oxygen equivalents required for complete oxidation of the substrates taken up by the kidney of fed rats exceeds, or is in agreement with, the published values (Weinstein & Szyjewick, 1976) of renal 0 2 consumption in the rat in vivo.…”

“…The preferential utilization of acetoacetate in the fed state may be due to its higher blood concentration (Elhamri et al 1993). It should be noted that the capacity or affinity of the apical transporter of ketone bodies did not change in brush-border-membrane vesicles prepared from starved rats (Barac-Nieto, 1986).…”

“…Together with the stimulation of unidirectional glutamine utilization, this may contribute to the increased net glutamine utilization observed in the kidney of starved rats (Elhamri et al 1993). Inhibition of glutamine utilization and, therefore, of glutamine oxidation by P-hydroxybutyrate in the fed state observed by Goldstein et al (1980Goldstein et al ( , 1982 is probably reduced in the starved state because, under ketotic conditions, the rat kidney does not appear to be sensitive to the inhibitory effects of ketone bodies.…”

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

“…After catheterization of a carotid artery, blood was withdrawn for measurement of blood acidbase parameters with a blood microsystem acid base analyzer (model BMS 3; Radiometer, Copenhagen, Denmark) and blood ketone-body levels as described previously (21); plasma was also separated by centrifugation at 4°C for measurement of cAMP and corticosterone levels. Then, the kidneys were removed and weighed and placed in ice-cold Krebs-Henseleit medium.…”