Effect of insulin on renal phosphorus handling in the rat: interaction with PTH and nicotinamide.
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.
D000818:Animals; D001692:Biological Transport; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D005919:Glomerular Filtration Rate; D007328:Insulin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010758:Phosphorus / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007328:Insulin; D010281:Parathyroid Hormone; D009243:NAD; D009536:Niacinamide; D010758:Phosphorus; D000242:Cyclic AMP