Cardiac microtubules are more resistant to chemical depolymerisation in streptozotocin-induced diabetes in the rat.
Evidence exists for a specific diabetic cardiomyopathy independent of concurrent vascular disease. Our aim was to test the hypothesis that a change in the microtubular cytoskeleton may contribute to cardiac dysfunction in type-1 diabetes. Resting sarcomere length and characteristics of unloaded shortening were measured in ventricular myocytes from rats 2 months after injection of streptozotocin (STZ). Microtubular density and organisation were assessed using immunofluorescence confocal microscopy and the effects of microtubule disruption by colchicine on shortening and microtubules were examined. Diabetic myocytes showed a significant reduction in resting sarcomere length and a 30% increase in time to peak shortening. The microtubule disruptor colchicine (10 micromol/l) had no effect on the amplitude or kinetics of shortening in myocytes from control or diabetic rats. Cardiac microtubular density and organisation were similar in control and diabetic animals, yet although colchicine significantly reduced microtubule density in control myocytes, microtubules in diabetic myocytes were resistant to its effects. These observations of an increase in microtubular stability in STZ-diabetes of 2 months duration imply a disruption to the normal balance between populations of dynamic and drug-stable microtubules. Such disruption has been observed in other pathological conditions and may contribute to diabetic cardiomyopathy.
Howarth
F C
FC
Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, UAE.
Qureshi
M A
MA
White
E
E
Calaghan
S C
SC
D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D011108:Polymers; D003078:Colchicine