# Alcohol, Retinoids and Pancreas Biology

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $192,375

## Abstract

ABSTRACT
We are proposing to investigate how chronic alcohol consumption induces pancreatitis and diabetes and the role
that retinoids (vitamin A and its natural metabolites) may have in this process. Mice will be fed either the alcohol-
containing or the isocaloric control Lieber-DeCarli diet. Pancreatitis will be induced in these mice by the use of
high doses of caerulein as described in the literature. Pancreatic health and functions, both endocrine and
exocrine, along with possible disruptions of pancreatic retinoid levels and actions, will be assessed. Our studies
will employ wild type mice and an induced mutant mouse model that lacks pancreatic retinoid stores, lecithin:
retinol acyltransferase-deficient (Lrat-/-) mice. The overall hypothesis that will be tested is that chronic alcohol
consumption impairs pancreatic retinoid metabolism and actions, both in the exocrine pancreas and in
pancreatic islets, and that these impairments contribute to alcohol's effect on pancreatic disease and
dysfunction. We propose 2 Specific Aims.
In Specific Aim 1, we will investigate the effects of chronic alcohol consumption on the pancreas, focusing on
the relationship between alcohol-dependent experimentally induced chronic pancreatitis and how this influences
and is influenced by pancreatic retinoid stores. Here we will identify how chronic alcohol-feeding affects the
development of pancreatitis in mice that possess normal pancreatic retinoid stores and in mice that possess no
retinoid stores in their pancreatic stellate cells (PSCs). Since the loss of PSC retinoid stores is associated with
the development of pancreatic fibrosis and pancreatitis, we expect to establish directly a role for pancreatic
retinoid stores in slowing or blocking the development of alcohol-induced pancreatic disease.
In Specific Aim 2, we will explore the effects of chronic alcohol consumption on the endocrine pancreas,
focusing specifically on the effect of alcohol-induced changes in pancreatic islet functions and how this is
associated with all-trans-retinoic acid (ATRA) signaling. ATRA is required for maintaining normal glucose
stimulated insulin secretion from the beta-cells of pancreatic islets. Our preliminary data suggest a role for ATRA
signaling in glucagon secretion from the alpha-cells of pancreatic islets. Here, we are proposing to investigate
how alcohol-induces the loss of normal pancreatic endocrine functions and whether this involves disruption of
normal ATRA signaling.
Collectively, the research we are proposing will extend understanding of the toxic effects of alcohol on the
pancreas.

## Key facts

- **NIH application ID:** 10023244
- **Project number:** 5R21AA028110-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** WILLIAM S BLANER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,375
- **Award type:** 5
- **Project period:** 2019-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023244

## Citation

> US National Institutes of Health, RePORTER application 10023244, Alcohol, Retinoids and Pancreas Biology (5R21AA028110-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10023244. Licensed CC0.

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