Cardiomyocyte dysfunction in insulin-resistant rats: a female advantage

Area of Science:

• Cardiovascular Physiology
• Metabolic Disease Research
• Sex-Based Biology

Background:

• Insulin resistance and prediabetes are linked to cardiomyocyte dysfunction.
• Sex-related differences in metabolic and cardiovascular disease progression are increasingly recognized.
• Understanding these differences is crucial for targeted therapeutic strategies.

Purpose of the Study:

• To investigate sex-specific differences in the development of cardiomyocyte dysfunction in prediabetic, insulin-resistant rats.
• To explore the role of intracellular calcium (Ca2+) handling in sex-related cardiac dysfunction.
• To determine if females exhibit cardioprotective mechanisms during early stages of insulin resistance.

Main Methods:

• Male and female rats were fed a high-sucrose diet to induce insulin resistance.
• Mechanical properties of isolated ventricular myocytes were assessed using high-speed video edge detection.
• In vitro interventions manipulated intracellular Ca2+ to evaluate its contribution to dysfunction.

Main Results:

• Sucrose-fed males exhibited significantly slower myocyte shortening and relengthening compared to controls.
• Females showed slower relengthening only, with a delayed onset of dysfunction (10 vs. 7 weeks in males).
• Myocytes from male rats required twice the extracellular Ca2+ to normalize function compared to females, indicating impaired Ca2+ handling.

Conclusions:

• Altered Ca2+ handling contributes to abnormal excitation-contraction coupling in insulin-resistant rat myocytes.
• Female rats appear to possess cardioprotection during early prediabetic stages, with delayed and milder cardiomyocyte dysfunction.
• While females show a tighter temporal coupling of metabolic and functional dysfunctions, males experience more rapid cardiac impairment.