# Roles of NAD+ metabolism in diabetic cardiomyopathy

> **NIH NIH P20** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $349,600

## Abstract

Diabetes is one of the major risk factors of heart failure and is characterized by a loss of metabolic control. Heart
failure is the main cause of death for diabetic patients. Literature and pilot studies support that NAD+ redox
imbalance promotes diabetic cardiomyopathy. However, mechanisms by which altered NAD+ metabolism
contributes to diabetic cardiomyopathy are far from established. This project aims to dissect how diabetic stress
alters NAD+ metabolism, and in turn promotes cardiac dysfunction. Our pilot studies show that up-regulated
nicotinamide riboside kinase (NMRK) could be a pathogenic mechanism of altered NAD+ metabolism in diabetic
hearts. In Aim 1, we will use targeted analyses of metabolites and transcripts involved in NAD+ metabolism to
determine how NMRK up-regulation regulates NAD+ metabolism in cardiomyocytes. We will determine the
pathogenic significance of NMRK up-regulation to the progression of diabetic cardiomyopathy using adeno-
associated virus-mediated over-expression in diabetic mice. Our pilot data identify that acetylation of calmodulin-
dependent protein kinase II (CaMKII), a key kinase regulating heart function, may contribute to diabetic
cardiomyopathy. In Aim 2, we will over-express acetylation mutants, and test the hypothesis that acetylation of
CaMKII regulates cardiomyocyte and mitochondrial function in vitro, and diabetic cardiomyopathy in vivo. This
project will explore an emerging paradigm that NAD+ metabolism regulates diabetic cardiomyopathy. The long-
term goal is to identify new therapeutic targets to treat cardiac dysfunction induced by diabetes, especially for
diastolic dysfunction that is a growing epidemic, and has no specific treatment regimen.

## Key facts

- **NIH application ID:** 10090980
- **Project number:** 1P20GM139763-01
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Chi Fung Lee
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,600
- **Award type:** 1
- **Project period:** 2021-02-05 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090980

## Citation

> US National Institutes of Health, RePORTER application 10090980, Roles of NAD+ metabolism in diabetic cardiomyopathy (1P20GM139763-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10090980. Licensed CC0.

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