Sex differences in ventricular muscle energetics in a type 2 diabetic rat model

Sex differences in cardiac function under diabetic conditions have been extensively studied. However, the impacts of type 2 diabetes on cardiac energetics between sexes remain poorly defined. Likewise, whether sex-specific differences in cardiac efficiency reported at the whole heart level manifest at the muscle level is uncertain. This study is the first to assess sex-specific cardiac energetics in type 2 diabetes by directly measuring heat production in isolated rat left ventricular trabeculae. Induction of diabetes in Wistar rats by a high-fat diet (23.5% kcal vs. 5% kcal from fat) and low-dose streptozotocin (30 mg/kg) was assessed through measurements of fasting blood glucose and glucose tolerance, and plasma biomarkers. Mechanoenergetics of isolated trabeculae were characterised using our work-loop calorimeter at body temperature. Experiments were conducted under loading conditions of varying muscle lengths, contraction modes, and afterloads. Force, muscle length, and heat output were simultaneously recorded. Metrics including twitch kinetics, shortening, mechanical work, activation heat, and cross-bridge heat were extracted, and mechanical efficiency was estimated and evaluated over a wide range of loading conditions. At the organism level, diabetic rats exhibited increased blood glucose levels and impaired glucose handling. While diabetes caused sex-specific effects on body mass, corticosterone, plasma insulin, and biomarkers, our results at the muscle level showed no effects of diabetes on any measured indices of cardiac mechanoenergetics and, hence, mechanical efficiency, in either sex. Effects of type 2 diabetes do not manifest in the mechanoenergetic functional performance of isolated cardiac muscles, even when challenged to a wide range of loading conditions. This conclusion is upheld in both male and female rats. These findings underscore the need for assessing cardiac function beyond the muscle level, as muscle-specific thermodynamics in diabetes may not be captured from systemic whole-organism measurements.