# Regulation of gastrointestinal hormone signaling and metabolism by Neuromedin U

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $401,098

## Abstract

ABSTRACT
 In obesity and type 2 diabetes mellitus (T2D), polyhormonal dysregulation can culminate in a relative
insulin-deficient state. Indirect evidence has recently accumulated for an enteric hormone (called a decretin)
that suppresses insulin and enhances glucagon output to promote T2D. A fundamental advance for the field
would be the identification of native hormones that normally regulate insulin and glucagon production and
secretion by pancreatic islet cells. We recently identified an enteroendocrine decretin signaling pathway in the
fruit fly Drosophila melanogaster regulated by nutrient availability, and essential for lipid, glucose and insulin
balance. We demonstrated from in vitro studies that the mammalian peptide hormone Neuromedin U (Nmu)
and its cognate G protein-coupled receptor, Nmu Receptor 1 (NmuR1) have similar functions. Nmu is
produced in enteroendocrine cells concentrated in the stomach, duodenum and ileum. In this proposal we
outline several original and novel approaches to investigate how the ligand-receptor pair Nmu/NmuR1 regulate
gastrointestinal hormone output.
 To address these fundamental questions in both in mice and humans, we propose Specific Aims to: 1.
Assess the requirement for enteric Nmu in mouse metabolic homeostasis. 2. Decode Nmu signal transduction
mechanisms by G proteins and NmuR1 in pancreatic islets. 3. Identify mechanisms regulating NMU signaling
in human islets
 This proposal is also notable for technical innovations in each Aim, including construction of multiple novel
mouse strains, and use of new ELISAs to investigate Nmu regulation in mice and humans. Collectively, these
state-of-the-art approaches will generate major new insights into the cellular and molecular mechanisms
controlling enteroendocrine regulation of metabolism in physiological settings. At a fundamental level, our work
should establish regulatory paradigms that interconnect metabolic signaling and regulation of crucial
gastrointestinal hormones. Thus, our work should have broad impact by suggesting strategies to diagnose,
stratify risk, and treat subsets of humans with diabetes mellitus or important pre-diabetic conditions like obesity
and impaired glucose tolerance.

## Key facts

- **NIH application ID:** 10131192
- **Project number:** 5R01DK107507-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Seung K Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,098
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131192

## Citation

> US National Institutes of Health, RePORTER application 10131192, Regulation of gastrointestinal hormone signaling and metabolism by Neuromedin U (5R01DK107507-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10131192. Licensed CC0.

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