APStracts 2:0430H, 1995.

Differential stimulation of na+-pump activity by insulin and nitric oxide in rabbit aorta. Gupta, Sandeep, Krista Phipps, and Neil B. Ruderman. Diabetes and Metabolism Unit, Boston University School of Medicine, Boston, MA 02118

APStracts 2:0430H, 1995.

The effect of insulin on Na+-pump activity, measured as ouabain -sensitive 86Rb-uptake (OS), was studied in the rabbit aorta. In the absence of insulin, incubation of endothelium-intact (EI) rings for 3 hours in a medium containing a high concentration of glucose (44 mM) decreased OS by 42% compared to that observed at 5.5 mM glucose. Addition of insulin (0.1-10 mU/ml) increased OS at both glucose concentrations and eliminated the differences between the groups. Insulin also increased OS in both EI and endothelium-denuded (ED) rings in the presence of the nitric oxide (NO) synthase inhibitor, N -monomethyl arginine. Removal of the endothelium before the incubations did not diminish the insulin-induced increase in OS, which was concentration-dependent. The NO donor, sodium nitroprusside (SNP), increased OS in ED rings, and its effect and that of insulin were additive. Phorbol 12-13 dibutyrate (PDB), a direct activator of protein kinase C (PKC), also increased OS in ED rings; however, its effect and that of insulin were not additive. The PKC inhibitor bisindolylmaleimide (BIM) totally inhibited insulin-induced, but not SNP-induced, increase in OS. These 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, it is independent of endothelium -derived NO, and it is presumably mediated by an increase in PKC activity. In contrast, activation of the Na+-pump by NO appears to be independent of PKC.

Received 5 July 1995; accepted in final form 11 September 1995.
APS Manuscript Number H614-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95