# The Role of Ceramides in the Pancreatic Beta Cell

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $562,220

## Abstract

SUMMARY
This proposal explores the hypothesis that sphingolipids such as ceramides serve as common, cell-autonomous
signals that impair beta cell function and contribute to the development of type 1 and type 2 diabetes. The idea
is predicated upon data presented herein showing that the administration of a pharmacological inhibitor of
ceramide biosynthesis to rodents preserves the beta cell and prevents the development of both forms of the
disease (i.e. in Zucker Diabetic Fatty rats as well as Non-Obese Diabetic mice). The theory is further supported
by studies in human and mouse islets implicating ceramides as intermediates linking saturated fatty acids and
inflammatory cytokines to the impairment of insulin secretion, mitochondrial function, and beta cell survival. We
will evaluate this hypothesized role for ceramides and its metabolites in the pancreatic islet through the following
aims:
· First, we will study new mouse models allowing for the conditional, beta cell-specific modulation of genes
 involved in ceramide synthesis or degradation, allowing us to determine whether the lipids are either (a)
 necessary or (b) sufficient for beta cell failure and the onset of frank hyperglycemia.
· Second, we will test the efficacy of a new class of ceramide synthesis inhibitors targeting dihydroceramide
 desaturase-1 as therapeutics that improve insulin secretion and prevent type 1 or type 2 diabetes in
rodents.
· Third, we will determine the mechanisms through which ceramides impair the function of mouse and
 human islets. We will test a hypothesized role for ceramides as drivers of metabolic reprogramming using
 state-of-the-art metabolic tracing, mitochondrial phenotyping, and cell function assays.
Findings obtained from these studies could uncover new nutrient-sensing and/or inflammatory mechanisms that
modulate islet function, survival and growth. Moreover, the translational component of this work could lead to
the development of new therapeutic alternatives for preventing or treating diabetes.

## Key facts

- **NIH application ID:** 10467400
- **Project number:** 1R01DK130296-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** WILLIAM L HOLLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $562,220
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467400

## Citation

> US National Institutes of Health, RePORTER application 10467400, The Role of Ceramides in the Pancreatic Beta Cell (1R01DK130296-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10467400. Licensed CC0.

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