# Human iPSC Model to Elucidate Metabolic Interplay in Diabetic Cardimyopathy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $672,653

## Abstract

Project Summary
Type 2 diabetes (T2D) is a leading cause of death nationwide with 65% of mortality due to cardiovascular
disease. The term “diabetic cardiomyopathy (T2DCM)” refers to a condition with adverse myocardial structural
changes, in the absence of hypertension and vascular pathology. Although T2D and CVD are tightly intertwined,
we lack a deeper understanding of T2DCM at the molecular and cellular levels. In recent years, sodium-glucose
cotransporter-2 (SGLT2) inhibitors have emerged as a promising therapeutic for T2DCM, but the precise
protective mechanisms in cardiomyocytes, fibroblasts, and endothelial cells which construct the cardiac
microenvironment remain incompletely understood. In this multi-PI R01 renewal, our team will elucidate the
mechanisms of metabolic interplay within and between cardiovascular cells which confer cardiac protection by
SGLT2 inhibition. We will harness induced pluripotent stem cell (iPSC) technology to generate diabetic models
of cardiovascular cell types for cellular and metabolic phenotyping of SGLT2 inhibition in vitro (Aim 1). We will
construct iPSC-derived engineered heart tissues for functional phenotyping and proteomic determination of the
SGLT2 inhibitor protein interactome (Aim 2). Afterward, we will validate cardioprotective mechanisms in a
diabetic mouse model at single-cell resolution (Aim 3). In summary, understanding the exact role and mechanism
of SGLT2 inhibition in T2DCM may contribute to finding new therapeutic modalities for the treatment of metabolic
heart diseases.

## Key facts

- **NIH application ID:** 10885206
- **Project number:** 5R01HL146690-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ronglih Liao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $672,653
- **Award type:** 5
- **Project period:** 2019-04-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885206

## Citation

> US National Institutes of Health, RePORTER application 10885206, Human iPSC Model to Elucidate Metabolic Interplay in Diabetic Cardimyopathy (5R01HL146690-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885206. Licensed CC0.

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