Key result
In a rat model of type I diabetes, diabetic rats showed lower maximum shortening velocity, prolonged timing parameters, and increased sarcomere length and crossbridge density.
Why the study?
It was unknown whether diabetes-associated altered ventricular function in type I diabetes results from changes in acto-myosin interactions and sarcomere rearrangement.
In a type I diabetic rat model, sarcomere modifications including increased length and crossbridge density appear to act as compensatory mechanisms that preserve systolic function despite early signs of diabetic cardiomyopathy.
Hypothesis-generating for sarcomeric changes in diabetic cardiomyopathy; requires human validation before clinical relevance.
NEW FINDINGS: What is the central question of this study? In the papillary muscle from type I diabetic rats, does diabetes-associated altered ventricular function result from changes of acto-myosin interactions and are these modifications attributable to a possible sarcomere rearrangement? What is the main finding and its importance? For the first time, we showed that type-I diabetes altered sarcomeric ultrastructure, as seen by transmission electron microscopy, consistent with physiological parameters. The diabetic condition induced slower timing parameters, which is compatible with a diastolic dysfunction. At the sarcomeric level, augmented β-myosin heavy chain content and increased sarcomere length and crossbridges' number preserve myocardial stroke and could concur to maintain the ejection fraction. ABSTRACT: We investigated whether diabetes-associated altered ventricular function, in a type I diabetes animal model, results from a modification of acto-myosin interactions, through the in vitro recording of left papillary muscle mechanical parameters and examination of sarcomere morphology by transmission electron microscopy (TEM). Experiments were performed on streptozotocin-induced diabetic and age-matched control female Wistar rats. Mechanical isometric and isotonic indexes and timing parameters were determined. Using Huxley's equations, we calculated mechanics, kinetics and energetics of myosin crossbridges. Sarcomere length and A-band length were measured on TEM images. Type I and III collagen and β-myosin heavy chain (MHC) expression were determined by immunoblotting. No variation in resting and developed tension or maximum extent of shortening was evident between groups, but diabetic rats showed lower maximum shortening velocity and prolonged timing parameters. Compared to controls, diabetics also displayed a higher number of crossbridges with lower unitary force. Moreover, no change in type I and III collagen was associated to diabetes, but pathological rats showed a two-fold enhancement of β-MHC content and longer sarcomeres and A-band, detected by ultrastructural morphometry. Overall, these data address whether a preserved systolic function accompanied by an altered diastolic phase results from a recruitment of super-relaxed myosin heads or the phosphorylation of the regulatory light chain site in myosin. Although the early signs of diabetic cardiomyopathy were well expressed, the striking finding of our study was that, in diabetics, sarcomere modification may be a possible compensatory mechanism that preserves systolic function.
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Isola et al. (2021) studied Type I diabetes. Streptozotocin-induced type I diabetes vs. Age-matched control female Wistar rats was evaluated on Left papillary muscle mechanical parameters and sarcomere morphology. In a rat model of type I diabetes, diabetic rats showed lower maximum shortening velocity, prolonged timing parameters, and increased sarcomere length and crossbridge density.
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