# The role of O-linked N-Acetylglucosamine Homeostasis in Pancreatic Beta-cell Development and Function

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $385,000

## Abstract

Type 2 diabetes (T2D) is the most common chronic disease affecting human health. Recent longitudinal and genome-wide association studies provide strong evidence that the ability of pancreatic β-cells to fulfill insulin demand through development, growth, survival, and function is a key determinant of whether an individual will develop T2D ! under various nutrient conditions. However, there are no effective clinical treatments that target β-cell growth and maintenance of their differentiated identity as insulin producing-cells. We propose that OGT (O-GlcNAc Transferase), a nutrient-sensor expressed at a very high level in β-cells, has key developmental regulatory properties and the ability to integrate signaling networks to regulate β-cell plasticity in response to insulin demand and nutrient stress. OGT is the sole enzyme adding a single O-GlcNAc post-translational modification (O-GlcNAcylation) onto proteins to orchestrate and fine-tune glucose metabolism, and β-cell growth and maintenance of identity under stress responses to nutrient changes and hormonal cues. We hypothesize that OGT tightly controls the O-GlcNAcylation state of downstream targets, including Pdx1, to promote β-cell development and function. Thus, our long-term goal is to define the mechanisms of how OGT integrates signaling networks impinging on β-cell plasticity (development and identity) to promote functional β-cells. We will test our hypothesis with the following Aims: 1. To establish the molecular mechanisms of how OGT regulates β-cell development and mass. 2. To delineate the mechanisms of how OGT regulates β-cell mass and identity under metabolic stress. The impact of this grant will show the central role of OGT in β-cell development and mass maintenance, and illustrate the translational relevance of OGT during time windows critical to metabolic health . Finally, these results will advance the field of β-cell biology and will open new horizons for therapies for patients with diabetes.

## Key facts

- **NIH application ID:** 10158468
- **Project number:** 5R01DK115720-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Emilyn Alejandro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158468

## Citation

> US National Institutes of Health, RePORTER application 10158468, The role of O-linked N-Acetylglucosamine Homeostasis in Pancreatic Beta-cell Development and Function (5R01DK115720-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158468. Licensed CC0.

---

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