Sex differences in cardiac energetics in type 2 diabetic rat ventricular muscle

Sex differences in cardiac energetics in type 2 diabetic rat ventricular muscle | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sex differences in cardiac energetics in type 2 diabetic rat ventricular muscle Maryam Rahmani, Toan Pham, Linley Nisbet, David Crossman, Kenneth Tran, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6858047/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Oct, 2025 Read the published version in Cardiovascular Diabetology – Endocrinology Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Background: 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. Methods: Induction of diabetes by a high-fat diet (23.5% kcal vs 5% kcal from fat) and low dose streptozotocin (30 g/kg) was assessed through measurements of fasting blood glucose and glucose tolerance, and plasma biomarkers. Mechano-energetics 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. Results: At the organism level, the diabetic rats exhibited increased blood glucose levels and impaired glucose handling. While diabetes caused sex specific effects on rat 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. Conclusions: 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. Cardiac Efficiency Type 2 Diabetes Heat Production highfat diet Cardiac Mechanoenergetics Full Text Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Cite Share Download PDF Status: Published Journal Publication published 01 Oct, 2025 Read the published version in Cardiovascular Diabetology – Endocrinology Reports → Version 1 posted Editorial decision: Revision requested 04 Jul, 2025 Reviews received at journal 04 Jul, 2025 Reviews received at journal 30 Jun, 2025 Reviewers agreed at journal 25 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers invited by journal 24 Jun, 2025 Editor assigned by journal 23 Jun, 2025 Submission checks completed at journal 23 Jun, 2025 First submitted to journal 09 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6858047","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476301106,"identity":"5d4e2c8e-39dc-48af-8a9d-549b841f9e83","order_by":0,"name":"Maryam 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