Effects of endurance training on the gluconeogenic capacity of periportal and perivenous hepatocytes.

This study was undertaken to assess the effect of 8 weeks of endurance training (treadmill, last 4 weeks: 60 min at 26 m/min, 8-10% grade) on the gluconeogenic capacity of periportal (PP-H) and perivenous (PV-H) hepatocytes of overnight fasted rats. Isolated PP-H and PV-H, obtained by selective destruction after liver perfusion with digitonin and collagenase, were incubated with saturating concentrations of a mixture of lactate and pyruvate (20:2 mM; Lac+Pyr) or alanine (20 mM; Ala) to determine the glucose production flux (J(glucose)) in the incubation medium. Endogenous J(glucose) as well as J(glucose) from substrates were significantly higher (P<.05) in PP-H than PV-H in the untrained state. Following training, a selective increase (P<.05) in J(glucose) from endogenous substrates and from Lac+Pyr was observed in PV-H only, resulting in the disappearance (P>.05) of the difference of J(glucose) between PP-H and PV-H. It is concluded that the increase in the gluconeogenic capacity of the liver following endurance training is first observed in PV-H.

Role of parathyroid hormone in the downregulation of liver cytochrome P450 in chronic renal failure.

Chronic renal failure (CRF) is associated with a decrease in drug metabolism secondary to a decrease in liver cytochrome P450 (P450). The predominant theory to explain this decrease is the presence of factors in the blood of uremic patients. This study tested the hypothesis that parathyroid hormone (PTH) could be this factor. The objectives of this study were to determine (1) the role of PTH in the downregulation of hepatocyte P450 induced by rat uremic serum, (2) the role of PTH in the downregulation of liver P450 in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes. For this purpose, (1) hepatocytes were incubated with serum from rat with CRF that was depleted with anti-PTH antibodies or with serum from parathyroidectomized (CRF-PTX) rat with CRF, (2) the effect of PTX on liver P450 was evaluated in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes were determined. The depletion of PTH from CRF serum completely reversed the downregulating effect of CRF serum on P450 in hepatocytes. Addition of PTH (10(-9) M) to depleted CRF serum induced a decrease in P450 similar to nondepleted CRF serum. The serum of CRF-PTX rats had no effect on P450 in hepatocytes compared with CRF serum. Adding PTH to CRF-PTX serum induced a similar decrease in P450 as obtained with CRF serum. Finally, PTX prevented the decrease of liver P450 in rats with CRF. In summary, PTH is the major mediator implicated in the downregulation of liver P450 in rats with CRF.