Type I and II models of diabetes produce different modifications of K + currents in rat heart: role of insulin

1 Several K + currents were measured and compared in enzymatically dispersed ventricular myocytes from control and diabetic rats. 2 Diabetic conditions were established either with a single intravenous injection of streptozotocin (STZ, 100 mg kg −1 ; 6‐14 days duration) or by feeding with a fructose‐enriched diet for 4‐10 weeks. Both groups became hyperglycaemic, with the former having decreased and the latter having elevated levels of plasma insulin. These conditions therefore mimic type I (insulin‐dependent) and type II (non‐insulin‐dependent) diabetes mellitus, respectively. 3 As reported previously, a Ca 2+ ‐independent transient outward K + current, I t , was attenuated in the type I model. This was not observed in the type II model. The two models differed greatly in the changes observed in a quasi‐steady‐state K + current denoted I ss . In the STZ model I ss was substantially attenuated, whereas in the fructose‐fed model it was augmented. In both models, the background inwardly rectifying current, I K1 , was unchanged. Concomitantly, there was a substantial prolongation of the action potential in the STZ model but not in the fructose‐fed model. 4 Incubation of control myocytes with insulin (100 nM) for 5‐9 h caused a significant augmentation of I ss , with no effect on I t or on I K1 . Incubation of myocytes from STZ‐diabetic rats with insulin reversed the attenuation of I t , but not of I ss . 5 The effect of insulin was not blocked by wortmannin, an inhibitor of phosphatidylinositol 3‐kinase. However, inhibition of the mitogen‐activated protein kinase pathway with PD98059 prevented restoration of I t . Insulin action on I t may therefore involve changes in transcription or expression of channel proteins, rather than changes in cellular metabolism.