Inhibition of Protein Kinase C Restores Na+, K+‐ATPase Activity in Sciatic Nerve of Diabetic Mice

Abstract

We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na⁺, K⁺‐ATPase activity in the sciatic nerve of alloxan‐induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na⁺, K⁺‐ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na⁺, K⁺‐ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4–9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half‐life of ∼ 1 h.