AJP - Renal Physiology, Vol 249, Issue 4 610-F618, Copyright © 1985 by American Physiological Society
Effect of insulin on renal phosphorus handling in the rat: interaction with PTH and nicotinamide
J. Guntupalli, A. Rogers and E. Bourke
Previous studies suggested an antiphosphaturic action of insulin. However,
effects of parathyroid hormone (PTH), anti-natriuresis, or other variables
were not vigorously controlled. Recently it has been suggested that
nicotinamide restores phosphaturia in several antiphosphaturic states.
Clearance studies were therefore performed in acutely parathyroidectomized
rats to test the hypothesis that insulin abolishes the phosphaturic action
of PTH and that this effect is prevented by nicotinamide. Superimposition
of euglycemic hyperinsulinemia on PTH infusion (plasma insulin 19.1 +/- 2.7
vs. 9.8 +/- 1.1 microU/ml, P less than 0.05) during steady-state Pi
excretion decreased fractional excretion (FE) of Pi compared with
PTH-infused controls (3.16 +/- 0.61 vs. 18.02 +/- 0.81%, P less than
0.001). Renal cortical NAD+ was lower in the former than the latter group
(455 +/- 22 vs. 689 +/- 30 pmol/mg, P less than 0.01). Nicotinamide
pretreatment prevented the antiphosphaturic action of insulin and the
decrease in cortical NAD+ in both the presence and absence of exogenous
PTH. These studies offer direct evidence that in acutely
parathyroidectomized rats insulin can abolish the phosphaturic action of
PTH, independent of glomerular filtration rate, the filtered loads of Pi
and glucose, FENa+, and cAMP excretion, an effect that is prevented by
nicotinamide pretreatment. In the absence of nicotinamide pretreatment,
superimposition of insulin on PTH infusion was associated with a decrease
in renal cortical NAD+. A role for intracellular NAD+, probably indirect,
in the antiphosphaturic action of insulin is suggested.
