Type I and II diabetes models produced different modifications of K+ currents in rat ventricular myocytes, with insulin reversing the attenuation of I(t) in the Type I model via the MAPK pathway.
Type I and Type II diabetes models produce distinct alterations in cardiac K+ currents, with insulin playing a role in restoring specific currents via the MAPK pathway.
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 Iss. In the STZ model Iss was substantially attenuated, whereas in the fructose-fed model it was augmented. In both models, the background inwardly rectifying current, IK1, 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 Iss, with no effect on I(t) or on IK1. Incubation of myocytes from STZ-diabetic rats with insulin reversed the attenuation of I(t), but not of Iss. 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.
Shimoni et al. (Sun,) conducted a other in Type I and II diabetes models (rat heart). Streptozotocin (STZ) injection or fructose-enriched diet; Insulin incubation vs. Control myocytes was evaluated on K+ currents (I(t), Iss, IK1) and action potential duration. Type I and II diabetes models produced different modifications of K+ currents in rat ventricular myocytes, with insulin reversing the attenuation of I(t) in the Type I model via the MAPK pathway.