Type 1 diabetes leads to cytoskeleton changes that are reflected in insulin action on rat cardiac K+ currents

A sustained K+ current (I-ss) is attenuated in ventricular cells from strep tozotocin (STZ)-induced diabetic rats. The in vitro addition of insulin to isolated cells augments I-ss in a process that is blocked by disrupting eit her actin microfilaments (with cytochalasin D) or microtubules (with colchi cine). When these agents are added at progressively later times, the effect of insulin becomes evident in a time-dependent manner. I-ss is also augmen ted by insulin in control cells in a cytoskeleton-dependent manner. However , in contrast to diabetic cells, cytoskeleton-dependent augmentation of I-s s by insulin occurs at a considerably faster rate in control cells. Immunof luorescent labeling shows a reduced density of beta -tubulin in diabetic ce lls, particularly in perinuclear regions. In vitro insulin replacement or i n vivo insulin injections given to STZ-treated rats enhances beta -tubulin density. These results suggest an impairment of cytoskeleton function and s tructure under insulin-deficient conditions, which may have implications fo r cardiac function.