Kinetics of Glucose Decarboxylation in the Substrate-Limited Isolated Perfused Kidney

Abstract

Rat kidneys were perfused with a cell-free perfusate containing substrate-free albumin, different glucose concentrations (0.20–5.0 mmol/l), and uniformly labeled ¹⁴C-glucose. The rate of glucose decarboxylation (Q_ox), as a function of [glucose]_p, displayed saturation kinetics [V_max = 0.35 µmol/(g · min); K_m = 0.87mmol/l]; saturation occurred at [glucose]_p = 1.0–2.0mmol/l. Although the presence of as low as 0.2mmol/l of glucose significantly increased fractional sodium reabsorption (%T_Na), there was no correlation between [glucose]_p or Q_ox and %T_Na. However, free water clearance (C_H2O or C_H2O/GFR) was directly proportional to [glucose]_pand independent of Q_ox. We conclude that (1) in the absence of other substrates, renal glucose Q_oxsaturates at hypoglycemic levels of glucose and (2) glucose plays an important role in the generation of solute-free water, a role that is unrelated to glucose Q_ox.

Fuel selection by the kidney: adaptation to starvation

“…This glucose production probably masks, at the whole-organ level in vivo, the concurrent utilization of glucose by the distal segments of the nephron. Several authors have demonstrated that glucose can be metabolized by various preparations of the rat kidney (Underwood & Newsholme, 1967;Weidemann & Krebs, 1969;Hems & Gaja, 1972;Ross et al 1973;Anaizi & Cohen, 1991). 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.…”

“…The rates of substrate uptake or metabolite release measured are only net rates and do not take into account the possibility that synthesis and degradation of a given substrate occur simultaneously. Indeed, it is well established that whole rat kidney has the capacity to utilize glucose via glycolysis (Hems & Gaja, 1972;Cohen et al 1977;Anaizi & Cohen, 1991) and synthesize glucose via gluconeogenesis (Nishiitsuji et al 1967;Bowman, 1970;Hems & Gaja, 1972). Similarly, whole rat kidney can form lactate by glycolysis under aerobic or anaerobic conditions (Hems & Gaja, 1972;Bartlett et al 1984) and utilize lactate as a substrate (Nishiitsutji ef al.…”