Diabetes causes right ventricle mitochondria impairment

R. Vargiu

Investigation

;A. Casti

Member of the Collaboration Group

;F. Broccia

Member of the Collaboration Group

;F. Loy

Member of the Collaboration Group

;M. Isola

Member of the Collaboration Group

;R. Isola

Writing - Original Draft Preparation

2019-01-01

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Abstract

Type-I diabetes leads to cardiomyopathy, which has been also ascribed to alterations in mitochondrial physiology. Despite numerous investigations on this topic it is still not clear what mechanisms develop mitochondrial impairment. We investigated on bioenergetic, morphological and proteomic mitochondrial features in a rat model of type-I diabetes. Female Wistar rats were injected with 60mg/kg streptozotocin and after 19-20 weeks of diabetic condition we checked left or right ventricles (LV or RV) mitochondrial subsarcolemmal (SSM) or interfibrillar (IFM) subpopulations, for changes in: activity of fatty acid import enzymes, oxidative phosphorylation (OXPHOS), cristal ultrastructure, mitofilin and Connexin 43 content. In our animal model of type-I diabetes there is a mild impairment of OXPHOS in different complexes for IFM and SSM, but this is not due to alteration of ion homeostasis (same Cx43). Mitofilin decrease is not enough to result in a manifest cristae morphology alteration, but might indicate a start of cristae reorganization, which is not yet significant after 5 months of diabetes. Surprisingly, both SSM (especially RV ones) seemed to be more sensitive to higher lipid input since their OXPHOS is defective. Lastly, diabetic RV SSM impairment might lead to cardiomyopathy of RV, recently reported in Type-II diabetes.