# Beta-cell responses to oxidative stress and Type 1 diabetes

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $635,080

## Abstract

Type 1 diabetes (T1D) is an autoimmune disease resulting in pancreatic β-cell destruction due to the generation of reactive oxygen species (ROS), proinflammatory cytokines/chemokines, and T cell effector molecules. Recent evidence has shown that β-cell dysfunction is also an activate participant in T1D pathogenesis. We will compare pancreatic β-cell functional identity changes that occur with T1D-prone Non-obese Diabetic (NOD) mice with T1D-resistant NOD.Ncf1m1J mice unable to generate NADPH oxidase (NOX)-derived superoxide. We will examine how the absence of ROS in NOD.Ncf1m1J mice can regulate β-cell functional identity, interactions with immune cells, and delay in T1D. To corroborate our genetic mouse models, we will examine pancreatic β-cell responses following treatment with a pharmacological manganese metalloporphyrin antioxidant with human islets. Our overarching hypothesis is that ROS reduction will preserve or enhance β-cell functional identity, as defined by transcriptional signatures and insulin secretion in T1D-prone NOD mice and human islets. To address this hypothesis, the following independent and interrelated aims will be defined: (1) Define how genetic ablation of ROS preserves β-cell functional identity. (2) Determine whether the absence of ROS can decrease pancreatic β-cell-mediated inflammatory responses. (3) Determine whether antioxidant treatment preserves the function of mouse and human β-cells. The insights gained from our studies will increase our understanding of diabetes etiology and may also point to future strategies employing antioxidant compounds to preserve and/or replace the function of pancreatic β-cells.

## Key facts

- **NIH application ID:** 10154970
- **Project number:** 1R01DK126456-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Chad S Hunter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $635,080
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154970

## Citation

> US National Institutes of Health, RePORTER application 10154970, Beta-cell responses to oxidative stress and Type 1 diabetes (1R01DK126456-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10154970. Licensed CC0.

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