Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

ABSTRACT:

Background

The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation.

Methods

To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myoca

SUBMITTER: Chen YH 

PROVIDER: S-EPMC10612246 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature