# The Role of Polyamines and Hypusine in Beta-Cell Dysfunction

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2024 · $568,857

## Abstract

PROJECT ABSTRACT
There is a massive prevalence of diabetes in the U.S. with 34.2 million having diabetes, and 88 million adults
with prediabetes. Type 1 diabetes results from the autoimmune destruction of the islet β cell mediated in part by
β-cell dysfunction prior to autoimmune attack. Polyamine and hypusine production are important for the
translation of a subset of RNAs involved in the unfolded protein response, ER stress, and cytokine response in
the β cell. Our preliminary data suggests that the polyamine/hypusine pathway is involved in the translation of
proteins required for the response of the β cell to inflammation. Inhibition of two rate limiting enzymes along the
polyamine/hypusine pathway, either genetically or with small molecule inhibitors, results in a decrease of ER
stress leading to protection from β-cell death and ultimately type 1 diabetes. For this proposal we will use a
combination of mouse, and human models to understand how the polyamines and hypusine specifically alter the
β cell’s response to stress. We propose to study the role of polyamines and hypusine in specific mRNA translation
of proteins that are important to the maladaptive response of β-cell ER stress and hypothesis that polyamine
depletion leads to ER stress resolution, preserved β-cell function, and ultimately reduced T1D pathogenesis. To
test this hypothesis, we propose the following aims:
Aim 1: Interrogate the molecular mechanisms by which the polyamine/hypusine pathway contributes to β-cell
dysfunction and death.
Aim 2: Determine the role of β cell polyamine/hypusine pathway during autoimmunity and the development of
T1D.
Aim 3: Assess the efficacy of treatment with polyamine/hypusine blockade.
The primary impact of this proposal is the identification of mechanisms of the polyamine/hypusine pathway in β
cells during the diabetes pathogenesis.

## Key facts

- **NIH application ID:** 10802890
- **Project number:** 1R01DK135832-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Sarah A. Tersey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $568,857
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802890

## Citation

> US National Institutes of Health, RePORTER application 10802890, The Role of Polyamines and Hypusine in Beta-Cell Dysfunction (1R01DK135832-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802890. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*