Summary
The mechanism by which hyperglycaemia causes decreased (Na+, K+)-ATPase activity preventable by aldose reductase inhibitors and by raising plasma myo-inositol in specific tissues can be activated in vitro in normal rabbit aortic wall; it selectively inhibits a component of resting (Na+, K+)-ATPase activity maintained by a novel regulatory system through rapid basal phosphatidylinositol turnover (hydrolysis) in a discrete pool, which is replenished by a fraction of phosphatidylinositol synthesis that selectively requires myoinositol transport. A role for endogenously released adenosine in this regulatory system was examined. Adding adenosine deaminase or 8-phenyltheophylline, an adenosine receptor antagonist, selectively inhibited the component of (Na+, K+)-ATPase activity maintained by the regulatory system; when inhibited with adenosine deaminase this component was restored by 2-chloroadenosine, 5′-N-ethylcarboxamidoadenosine, and 1-oleoyl-2-acetylglycerol, but not by forskolin (which also did not inhibit this component). Adenosine deaminase inhibited the rapid basal turnover of the discrete phosphatidylinositol pool, and 2-chloroadenosine then stimulated its turnover. Raising medium glucose from 5 to 10–30 mmol/l inhibits the regulatory system by making myo-inositol transport at a normal plasma level inadequate to maintain the replenishment of the discrete phosphatidylinositol pool. 2-Chloroadenosine stimulation of the “adenosine-sensitive” component of (Na+, K+)-ATPase activity was inhibited in tissue incubated with 30 mmol/l glucose and myoinositol in a normal plasma level, but this effect was demonstrable when the medium myo-inositol was raised seven-fold. Hyperglycaemia-induced decreased (Na+, K+)-ATPase activity that is preventable by aldose reductase inhibitors and by raising plasma myo-inositol results from the inhibition of a novel adenosine-(Na+, K+)-ATPase regulatory system.
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Simmons, D.A., Winegrad, A.I. Elevated extracellular glucose inhibits an adenosine-(Na+, K+)-ATPase regulatory system in rabbit aortic wall. Diabetologia 34, 157–163 (1991). https://doi.org/10.1007/BF00418269
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DOI: https://doi.org/10.1007/BF00418269