Maximum Shortening Velocity and Power Are Reduced in a Human Cross-bridge Model of Type 2 Diabetes

Human cardiac trabeculae were studied to identify the effects of diabetes on passive and active tissue mechanical properties.The sensitivity of cross-bridge cycling kinetics to [ATP] and [P i ] was probed using small-amplitude sinusoidal perturbations in a custom-built device.The diabetic muscles produced lower active and passive stresses, and the complex modulus data revealed that they also had slower cross-bridge cycling kinetics.These data were used to parameterise metabolite-sensitive cross-bridge models representing diabetic and non-diabetic cohorts.These cross-bridge models were then integrated within a muscle model to simulate twitch dynamics and stress-length workloops.The diabetic model had slower twitch kinetics reduced maximum shortening velocity and reduced muscle shortening power.Simulation of changes in metabolic state revealed that, while increasing [P i ] reduced muscle shortening power in both groups, the reduction was less pronounced in the diabetic model.These results suggest the presence of a compensatory mechanism to mitigate the effects of metabolic dysfunction in the diabetic heart.