# Metabolic regulation of pancreatitis

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $362,250

## Abstract

Abstract
Acute pancreatitis is a debilitating disease that affects more than 280,000 people in the United States. A
hallmark of acute pancreatitis is systemic injury and multi-organ failure leading to mortality in 3-20% of
patients. There are currently no treatments for acute pancreatitis. Alcohol consumption is a major cause of
human acute pancreatitis and despite intensive investigation the pathogenesis of alcohol-induced pancreatitis
remains poorly understood. Evidence suggests that acinar cell injury is associated with mitochondrial
dysfunction leading to ATP depletion and prevention of mitochondrial damage or restoration of mitochondrial
function may limit pancreatitis. Phosphate availability is required for ATP synthesis. Clinical
hypophosphatemia is common in alcoholic patients and alcohol itself impairs dietary phosphate absorption. In
preliminary studies, we discovered that reduced serum phosphate levels in patients with acute pancreatitis are
associated with increased pancreatitis severity. We proposed that reduced phosphate availability may
predispose to alcohol-induced pancreatic injury and may be central to the development of alcoholic
pancreatitis. Our preliminary data indicate that alcohol rapidly induces pancreatitis when mice are fed a low
phosphate diet, consistent with the concept that hypophosphatemia sensitizes the pancreas to alcohol. The
current study is designed to test the hypothesis that alcohol-induced pancreatitis can be ameliorated by
phosphate administration. We will determine the contribution of hypophosphatemia to pancreatitis severity, the
protective effects of phosphate treatment in mouse models of pancreatitis, and the mechanisms underlying the
effects of hypophosphatemia on pancreatic injury. Successful completion of these studies will yield compelling
pre-clinical data for a novel, simple and effective treatment for pancreatitis that will provide the basis for a
clinical trial in humans.

## Key facts

- **NIH application ID:** 10028137
- **Project number:** 1R01DK125308-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rodger A. Liddle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,250
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028137

## Citation

> US National Institutes of Health, RePORTER application 10028137, Metabolic regulation of pancreatitis (1R01DK125308-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10028137. Licensed CC0.

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