# Mechanisms of Myocardial Infarction-induced insulin resistance

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $516,357

## Abstract

Myocardial infarction (MI) is the leading cause of mortality in the USA. Patients develop insulin resistance
after acute MI. In a mouse model of MI, we found coronary ligation significantly increased insulin resistance
in mice fed with either a chow diet or high fat diet. Recent studies have shown that MI-induced insulin
resistance has direct proatherogenic effects at the level of atherosclerotic plaques leading to a series of
cellular atherogenic events and plaque progression. But the mechanistic underpinnings of insulin resistance
after MI are not explored. We have recently shown that MI increases production of inflammatory monocytes,
which can infiltrate visceral adipose tissue (VAT) and differentiate into macrophages. Consistently, our
preliminary data revealed that MI-induced insulin resistance was associated with accumulation of CX3CR1+
CCR2+ monocyte-derived macrophages in VAT. We hypothesize that the influx of monocyte-derived
macrophages into VAT after MI creates an inflammatory milieu, resulting in insulin resistance. We will test
the hypothesis in three specific aims. 1.We will investigate the dynamics of macrophage subsets in VAT
after MI. We will use flow cytometry and intravital microscopy to investigate monocyte accumulation in VAT
after MI. 2.To test the mechanisms of MI-induced insulin resistance, we will investigate if loss of M-CSF
after MI leads to insulin resistance. Our preliminary experiments showed that coronary ligation in mice
reduced systemic levels of M-CSF, a cytokine responsible for tissue resident macrophage survival. 3. We
will investigate if the accumulation of monocyte-derived macrophages induces insulin resistance after MI
using a mouse strain of tamoxifen-inducible CX3CR1. Furthermore, since monocyte-derived VAT
macrophages express high levels of IL-1β, we will use IL-1β neutralizing antibody to explore whether it can
improve insulin sensitivity. The proposed grant application will further our understanding of mechanisms
behind MI-induced insulin resistance and explore new therapeutic avenues.

## Key facts

- **NIH application ID:** 9880440
- **Project number:** 5R01HL143967-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Partha Dutta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,357
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880440

## Citation

> US National Institutes of Health, RePORTER application 9880440, Mechanisms of Myocardial Infarction-induced insulin resistance (5R01HL143967-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880440. Licensed CC0.

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