Differential stimulation of Na+ pump activity by insulin and nitric oxide in rabbit aorta.
The effect of insulin on Na+ pump activity, measured as ouabain-sensitive (OS) 86Rb uptake, was studied in the rabbit aorta. In the absence of insulin, incubation of endothelium-intact rings for 3 h in a medium containing a high concentration of glucose (44 mM) decreased OS 86Rb uptake by 42% compared with that observed at 5.5 mM glucose. Addition of insulin (0.1-10 microU/ml) increased OS86 86Rb uptake at both glycose concentrations and eliminated the differences between the groups. Insulin also increased OS 86Rb uptake in endothelium-intact and -denuded (ED) rings in the presence of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine. Removal of the endothelium before the incubations did not diminish the insulin-induced increase in OS 86Rb uptake, which was concentration dependent. The NO donor sodium nitroprusside increased OS 86Rb uptake in ED rings, and its effect and that of insulin were additive. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C (PKC), also increased OS 86Rb uptake in ED rings; however, its effect and that of insulin were not additive. The PKC inhibitor bisindolylmaleimide totally inhibited insulin-induced, but not sodium nitroprusside-induced, increases in OS 86Rb uptake. The results suggest that insulin activates the Na+ pump in the aorta and reverses the inhibition of the pump caused by hyperglycemia. This effect of insulin can occur at physiological concentrations, is independent of endothelium-derived NO, and is presumably mediated by an increase in PKC activity, In contrast, activation of the Na+ pump by NO appears to be independent of PKC.
Gupta
S
S
Diabetes and Metabolism Unit, Boston University School of Medicine, Massachusetts 02118, USA.
Phipps
K
K
Ruderman
N B
NB
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D012413:Rubidium / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D007328:Insulin; D009569:Nitric Oxide; D010042:Ouabain; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D012413:Rubidium