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

Human-centric cardiac models are needed that recapitulate mechanistic and functional changes in the type 2 diabetic myocardium for understanding disease pathogenesis and developing new therapies. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in 2D and 3D as engineered heart tissue (EHT), we aimed to model diabetic cardiomyopathy in cellulo. Taking an unbiased systems biology approach, our cellular models recapitulated the dysregulated pathways and functional derangement of diabetic cardiomyopathy. Three-dimensional EHT models showed contractile dysfunction akin to that seen in patients, with mechanistic and functional changes reversed with metformin. It is possible to generate translationally relevant hiPSC-CM models that mimic diabetic cardiomyopathy.

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Publication Details

Journal
Diabetes
Published
2025-09-16
DOI
https://doi.org/10.2337/db25-0204
Citations
1
Primary Topic
Cardiovascular Function and Risk Factors
Type
article
Field-Weighted Citation Impact
1.39

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article

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

Ryan D. Carter, Anandhakumar Chandran, Jack J. Miller, Charlotte Daly et al.
1 citations
Diabetes
Cardiovascular Function and Risk Factors
1.39
article

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

Ryan D. Carter, Anandhakumar Chandran, Jack J. Miller, Charlotte Daly, Carolyn A. Carr, Helen Christian, Ujang Purnama, Lisa C. Heather, Richard Mbasu, Francesca M. Buffa, Maxwell A. Ruby, Marcos Castro‐Guarda, Claudia N. Montes-Aparicio, Kirsti Brisk
article en
1 citations

Abstract

Human-centric cardiac models are needed that recapitulate mechanistic and functional changes in the type 2 diabetic myocardium for understanding disease pathogenesis and developing new therapies. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in 2D and 3D as engineered heart tissue (EHT), we aimed to model diabetic cardiomyopathy in cellulo. Taking an unbiased systems biology approach, our cellular models recapitulated the dysregulated pathways and functional derangement of diabetic cardiomyopathy. Three-dimensional EHT models showed contractile dysfunction akin to that seen in patients, with mechanistic and functional changes reversed with metformin. It is possible to generate translationally relevant hiPSC-CM models that mimic diabetic cardiomyopathy.

DiabetesVol. 74(11)
Aarhus University (DK), Aarhus University Hospital (DK), University of Oxford (GB), Novo Nordisk (Finland) (FI), Bocconi University (IT)
British Heart Foundation, Rosetrees Trust, Novo Nordisk
Openalex Percentile: Top 15%
Cardiovascular Function and Risk Factors
1.39
DOIOpen Access PDFOpenAlex
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Systems Biology and Functional Assessments of Human iPSC-Cardiomyocyte Models of Insulin Resistance Capture Key Hallmarks of Diabetic Cardiomyopathy — Ryan D. Carter, Anandhakumar Chandran, et al. · Diabetes (2025) | TGRS Research Map | TGRS