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The fast transient outward current, Ito,fast, is the most extensively studied cardiac K+ current in diabetic animals. Two hypotheses have been proposed to explain how type-1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced Ito,fast. Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart: Ito,slow, IKr, IKs, IKur, IKslow and IK1.We recorded cardiac action potentials and K+ currents in ventricular cells isolated from control and streptozotocin- or alloxan-induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence.Diabetes reduces the amplitude of Ito,fast, Ito,slow and IKslow, in ventricular myocytes from mouse and rabbit, with no effect on Iss, IKr or IK1. The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six-hour incubation of myocytes with insulin or pyruvate recovered current amplitudes and fluorescent staining. The activation of AMP-K reduced the same K+ currents in healthy myocytes and prevented the pyruvate-induced current recovery.Diabetes reduces K+ current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP-K secondary to deterioration in the metabolic status of the cells is responsible for K+ channel reductions.