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 streptozotocin (STZ)-induced diabetic rats. The in vitro addition of insulin to isolated cells augments I(ss) in a process that is blocked by disrupting either actin microfilaments (with cytochalasin D) or microtubules (with colchicine). When these agents are added at progressively later times, the effect of insulin becomes evident in a time-dependent manner. I(ss) is also augmented by insulin in control cells in a cytoskeleton-dependent manner. However, in contrast to diabetic cells, cytoskeleton-dependent augmentation of I(ss) by insulin occurs at a considerably faster rate in control cells. Immunofluorescent labeling shows a reduced density of beta-tubulin in diabetic cells, particularly in perinuclear regions. In vitro insulin replacement or in vivo insulin injections given to STZ-treated rats enhances beta-tubulin density. These results suggest an impairment of cytoskeleton function and structure under insulin-deficient conditions, which may have implications for cardiac function.
Shimoni
Y
Y
Department of Physiology and Biophysics, University of Calgary Health Sciences Centre, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. shimoni@ucalgary.ca
Rattner
J B
JB
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004553:Electric Conductivity; D019084:Fluorescent Antibody Technique, Indirect; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D009206:Myocardium / Q000648:ultrastructure; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
D007328:Insulin; D019384:Nucleic Acid Synthesis Inhibitors; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D014404:Tubulin; D015638:Cytochalasin D; D003513:Cycloheximide; D003078:Colchicine