Key result
Type 1 diabetes increased the vulnerability of the cardiac mitochondrial network to criticality, significantly reducing the delay time to depolarization compared to controls, an effect rescued by insulin.
Why the study?
It was sought to investigate whether mitochondrial criticality occurs in the chronic setting of type 1 diabetes.
Does insulin or redox-improving interventions reduce the vulnerability of cardiac mitochondrial networks to criticality in a type 1 diabetes guinea pig model?
Does insulin or redox-improving interventions reduce the vulnerability of cardiac mitochondrial networks to criticality in a type 1 diabetes guinea pig model?
In a guinea pig model of type 1 diabetes, the cardiac mitochondrial network is closer to criticality and more vulnerable to oscillations, which can be reversed by insulin or redox-improving interventions.
Should not yet change clinical practice in type 1 diabetes; hypothesis-generating for mitochondrial network vulnerability in diabetic cardiomyopathy.
Mitochondrial criticality describes a state in which the mitochondrial cardiac network under intense oxidative stress becomes very sensitive to small perturbations, leading from local to cell-wide depolarization and synchronized oscillations that may escalate to the myocardial syncytium generating arrhythmias. Herein, we describe the occurrence of mitochondrial criticality in the chronic setting of a metabolic disorder, type 1 diabetes (T1DM), using a streptozotocin (STZ)-treated guinea pig (GP) animal model. Using wavelet analysis of mitochondrial networks from two-photon microscopy imaging of cardiac myocytes loaded with a fluorescent probe of the mitochondrial membrane potential, we show that cardiomyocytes from T1DM GPs are closer to criticality, making them more vulnerable to cell-wide mitochondrial oscillations as can be judged by the latency period to trigger oscillations after a laser flash perturbation, and their propensity to oscillate. Insulin treatment of T1DM GPs rescued cardiac myocytes to sham control levels of susceptibility, a protective condition that could also be attained with interventions leading to improvement of the cellular redox environment such as preincubation of diabetic cardiac myocytes with the lipid palmitate or a cell-permeable form of glutathione, in the presence of glucose.
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Vetter et al. (2020) studied Type 1 Diabetes Mellitus. Streptozotocin-induced Type 1 Diabetes vs. Sham (vehicle) was evaluated on Delay time to first cell-wide mitochondrial depolarization (seconds) (p=0.011). Type 1 diabetes increased the vulnerability of the cardiac mitochondrial network to criticality, significantly reducing the delay time to depolarization compared to controls, an effect rescued by insulin.
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