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 led 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 Ca2+-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 Kf 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, J(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 J(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.