Y. Shimoni et al., TYPE-I AND TYPE-II MODELS OF DIABETES PRODUCE DIFFERENT MODIFICATIONSOF K-HEART - ROLE OF INSULIN( CURRENTS IN RAT), Journal of physiology, 507(2), 1998, pp. 485-496
1. Several K+ currents were measured and compared in enzymatically dis
persed ventricular myocytes from control and diabetic rats. 2. Diabeti
c conditions were established led either with a single intravenous inj
ection of streptozotocin (STZ, 100 mg kg(-1); 6-14 days duration) or b
y feeding with a fructose-enriched diet for 4-10 weeks. Both groups be
came hyperglycaemic, with the former having decreased and the latter h
aving elevated levels of plasma insulin. These conditions therefore mi
mic type I (insulin-dependent) and type II. (non-insulin-dependent) di
abetes mellitus, respectively. 3. As reported previously, a Ca2+-indep
endent 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 dif
fered greatly in the changes observed in a quasi-steady-state Kf curre
nt denoted I-ss. In the STZ model I-ss was substantially attenuated, w
hereas in the fructose-fed model it was augmented. In both models, the
background inwardly rectifying current, J(K1) was unchanged. Concomit
antly, there was a substantial prolongation of the action potential in
the STZ model but not in the fructose-fed model. 4. Incubation of con
trol myocytes with insulin (100 nM) for 5-9 h caused a significant aug
mentation of I-ss, with no effect on I-t or on J(K1). Incubation of my
ocytes 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 wor
tmannin, an inhibitor of phosphatidylinositol 3-kinase. However, inhib
ition of the mitogen-activated protein kinase pathway with PD98059 pre
vented restoration of I-t. Insulin action on I-t may therefore involve
changes in transcription or expression of channel proteins, rather th
an changes in cellular metabolism.