Systems Biology and Functional Assessments of Human iPSC-Cardiomyocyte Models of Insulin Resistance Capture Key Hallmarks of Diabetic Cardiomyopathy.

ABSTRACT: Human-centric models of diabetic cardiomyopathy (DbCM) are needed to provide mechanistic insights and translationally relevant therapeutic targets for patients with diabetes. A systems biology approach using insulin resistant (IR) two-dimensional (2D) human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and three-dimensional (3D) engineered heart tissue (EHT) provides a comprehensive evaluation of dysregulated pathways and determines suitability as a translationally relevant model of DbCM. Culturing hiPSC-CMs in 2D or 3D EHT in IR media induced insulin resistance and activated multiple pathways implicated in DbCM, including metabolic remodeling, mitochondrial dysfunction, extracellular matrix remodeling, endoplasmic reticulum stress, and blunted response to hypoxia, as as

SUBMITTER: Carter RD 

PROVIDER: S-EPMC12585165 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature