Streptozotocin-induced diabetes in rats elevated cyclophilin D at 4 weeks, but decreased by 12 weeks, suggesting early susceptibility to mPTP opening without overt histological damage.
RCT
Randomly assigned
In a rat model of STZ-induced diabetes with minimal insulin, early susceptibility to mPTP opening occurs before overt histological cardiac damage, highlighting the importance of model duration and insulin dosing in diabetic cardiomyopathy research.
The simultaneous characterization of histological alterations and distinct cell death pathways associated with diabetic cardiomyopathy (DCM) has not been comprehensively explored and may differ depending on the experimental model. We evaluated cardiac histological changes and markers of apoptosis, cell death associated with mitochondrial permeability transition pore (mPTP) opening (necrosis), and autophagy in early and advanced stages of streptozotocin (STZ)-induced diabetes in rats receiving insulin daily to prevent mortality while maintaining hyperglycemia. Adult male Sprague-Dawley rats (n = 4-5) were randomly assigned to receive STZ (diabetic group) or saline (mock) and followed up for 4 or 12 weeks. Hearts were processed for histological examination and immunohistochemical detection of active caspase-3, beclin-1, and cyclophilin D. STZ significantly increased glycemia at both time points, whereas body weight reduction was observed only at 12 weeks. No evidence of cardiac hypertrophy, fibrosis, or structural injury was detected in diabetic rats at either stage. Expression of caspase-3, beclin-1, and cyclophilin D decreased at 12 weeks compared with 4 weeks, regardless of treatment; however, cyclophilin D was elevated in diabetic hearts at 4 weeks. These results suggest an early susceptibility to mPTP opening under persistent hyperglycemia, despite the absence of overt histological damage. They also underscore the critical importance of insulin dosing and study duration when interpreting data from STZ-based models. Further studies are warranted to determine how even minimal insulin administration may shape the temporal dynamics of cell death during the progression of DCM.
Sáez et al. (Thu,) conducted a rct in Diabetic cardiomyopathy. Streptozotocin (STZ) and daily insulin vs. Saline (mock) was evaluated on Cardiac histological changes and markers of apoptosis, necrosis, and autophagy. Streptozotocin-induced diabetes in rats elevated cyclophilin D at 4 weeks, but decreased by 12 weeks, suggesting early susceptibility to mPTP opening without overt histological damage.