Cardiomyocyte dysfunction in insulin-resistant rats: a female advantage.
OBJECTIVE
The goal of this investigation was to determine whether there are sex-related differences in the development of cardiomyocyte dysfunction in prediabetic, insulin-resistant animals.


METHODS
Male and female rats were maintained on a high-sucrose diet for 5-11 weeks, and mechanical properties of isolated ventricular myocytes were measured by high-speed video edge detection. Several in vitro interventions were used to manipulate intracellular Ca(2+) in order to determine whether altered Ca(2+) availability contributes to the cardiomyocyte dysfunction.


RESULTS
Myocyte shortening and relengthening were significantly slower in sucrose-fed (insulin-resistant) males than in starch-fed (normal) male rats, whereas only relengthening was slower in sucrose-fed females when compared with normal females. Areas under the contraction and relaxation phases for sucrose-fed males were also significantly larger than in diet-matched females, and the slowed cardiomyocyte mechanics appeared earlier in males (7 vs 10 weeks). Prolonged relaxation was ameliorated in myocytes from sucrose-fed female rats by all interventions (i.e. 10(-8) mol/l isoprenaline, elevated extracellular Ca(2+), and higher rates of stimulation). Twice as much extracellular Ca(2+) (4 mmol/l) was required to restore normal time courses of contraction and relaxation in sucrose-fed males than in females, and mechanical responses to higher frequency stimulation remained impaired (slower) in some myocytes from sucrose-fed male rats.


CONCLUSIONS
These data suggest that in myocytes from insulin-resistant rats altered Ca(2+) handling occurs, contributing to abnormal excitation-contraction coupling; female rats seem to have some cardioprotection during early stages in the progression towards type 2 diabetes. Females show delayed onset and milder abnormalities in metabolic status and cardiomyocyte function, but with a much tighter temporal coupling of these dysfunctions.
Schwanke
M L
ML
College of Arts and Sciences, University of Maine at Farmington, Farmington, ME, USA.
Dutta
K
K
Podolin
D A
DA
Davidoff
A J
AJ
D000818:Animals; D001696:Biomechanical Phenomena; D004032:Diet; D019422:Dietary Sucrose / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007333:Insulin Resistance; D008297:Male; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D051381:Rats; D012727:Sex Characteristics
D019422:Dietary Sucrose