# Insulin Modulates Parasympathetic Nerve Control of Lungs

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $473,022

## Abstract

Project Summary:
Obesity increases the incidence and severity of asthma, but an incomplete understanding of the molecular
mechanisms underlying obesity-related asthma make it difficult prevent and treat this phenotype.
Parasympathetic nerves mediate one mechanism of airway hyperreactivity. These nerves provide dominant
autonomic control of airway tone and release acetylcholine (ACh), which activates M3 muscarinic receptors on
airway smooth muscle, causing contraction and bronchoconstriction. ACh release is controlled by inhibitory M2
muscarinic receptors on these nerves. Thus, airway hyperreactivity results from decreased neuronal M2
receptor function and subsequent increased ACh release. Our preliminary data show that obesity is associated
with increased bronchoconstriction in response to parasympathetic nerve stimulation, with reduced neuronal M2
receptor function, and that these effects are mediated by insulin even in the absence of inflammation. Thus, our
hypothesis is that increased insulin, as seen in obesity, binds to insulin receptors on airway
parasympathetic nerves resulting in airway hyperreactivity by reducing M2 muscarinic function on
parasympathetic nerves (thus increasing ACh release). We propose to test how insulin reduces M2
receptor expression and function, identify which insulin receptor and signaling pathways mediate neuronal M2
dysfunction and test whether manipulating insulin (with diet, oral anti-glycemic drugs and with an insulin binding
antibody) protects M2 receptor function and inhibits obesity induced airway hyperreactivity. This research is
significant because it has the potential to explain why obese patients with increased insulin, are more prone to
asthma and identify novel strategies, including control of insulin, and M3 selective muscarinic antagonists, that
may treat obesity-related asthma.

## Key facts

- **NIH application ID:** 9838774
- **Project number:** 5R01HL131525-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** ALLISON Deborah FRYER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,022
- **Award type:** 5
- **Project period:** 2016-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838774

## Citation

> US National Institutes of Health, RePORTER application 9838774, Insulin Modulates Parasympathetic Nerve Control of Lungs (5R01HL131525-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838774. Licensed CC0.

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