Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex.
Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D003864:Depression, Chemical; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D010281:Parathyroid Hormone; D005934:Glucagon; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP