# Role of fatty acid oxidation in islet beta-cell function

> **NIH NIH P20** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2020 · $221,999

## Abstract

Project Summary:
Type 1 diabetes mellitus (T1D) results from reduced total number or diminished function of insulin-producing
beta-cells within the pancreatic islets of Langerhans. How lipid metabolism influences the ability of the islet
beta-cells to secrete insulin, regulate glucose metabolism, and proliferate has been largely studied almost
exclusively in isolated islets using acute in vitro approaches. However, studies conducted in vitro have led to
differential and often conflicting results. Herein, we propose two novel mouse models that allow us to address
the role of lipid metabolism from two critical organelles to investigate targeted and specific outcomes in vivo.
This approach will allow us to answer the fundamental question: does inhibition of fatty acid oxidation in
pancreatic tissue, including islet beta-cells, contribute to alterations in beta-cell function observed during aging,
insulin resistance, and diabetes? To address this question, we will use mice lacking either carnitine
palmitoyltransferase-1a (CPT-1a; Aim 1), a mitochondrial gene, or Pex5 (peroxisomal gene; Aim 2) in
pancreatic and islet tissue. In Specific Aim 1, we will use the pancreas-specific deletion of the Cpt1a gene in
combination with low-fat and high-fat diets to determine whether limiting fatty acid oxidation enhances glucose
metabolism to support insulin secretion. In this experiment, we will also assess whether fatty acid oxidation is
critical for the expansion of beta-cells observed during states of insulin resistance in vivo. In Specific Aim 2, we
will limit fatty acid oxidation in the peroxisomal compartment, which regulates the metabolism of very long
chain fatty acids, to determine whether this enhances beta-cell function or promotes lipid storage to generate
metabolic stress and key features of lipotoxicity. These novel genetic approaches will provide critical insights
into the role of lipid oxidation during aging and obesity. Understanding the principles and mechanisms
underlying fatty acid oxidation on islet biology in vivo have important implications for suppressing, treating, and
curing obesity- and aging-associated metabolic diseases.

## Key facts

- **NIH application ID:** 9854388
- **Project number:** 1P20GM135002-01
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Susan J. Burke
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $221,999
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854388

## Citation

> US National Institutes of Health, RePORTER application 9854388, Role of fatty acid oxidation in islet beta-cell function (1P20GM135002-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9854388. Licensed CC0.

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