# Physiology/Pathophysiology of Vitamin B1 Transport in Pancreatic Acinar Cells

> **NIH NIH R01** · SOUTHERN CALIFORNIA INST FOR RES/EDUC · 2020 · $492,764

## Abstract

Vitamin B1 (thiamin) is indispensable for normal function/health of pancreatic cells due its critical roles in
oxidative energy metabolism, ATP production, and in maintaining normal cellular redox state. Low
intracellular level of thiamin leads to acute energy failure, oxidative stress, and impairment in mitochondrial
function. At the organ level, the metabolically active pancreas maintains high levels of thiamin, and deficiency
of the vitamin impairs its functions. The pancreas cannot synthesis thiamin endogenously; rather it obtains it
from circulation. The overall goal of this research program since its inception has been focused on developing
a comprehensive understanding of the molecular mechanisms involved in thiamin uptake by pancreatic acinar
cells (PACs) and the subsequent transport (compartmentalization) of its major intracellular form, i. e., thiamin
pyrophosphate (TPP), into mitochondria, how these processes are regulated, and how they are affected by
exposure to external/internal factors that are known to adversely affect the normal physiology/health of the
pancreas. We have addressed many of these issues, and in the current proposal aim at determining: i) the role
of microRNAs in post-transcriptional regulation of THTR-1, THTR-2, and the mitochondrial TPP transporter
(MTPPT) expression in PACS, and the uptake processes that they mediate; ii) whether THTR- 1 and THTR-2
of PACs have interacting partners that affect/regulate their physiology/cell biology; and iii) the effect of
specific factors that PACs are exposed to under certain pathophysiological conditions [pro-inflammatory
cytokines, and the bacterial lipopolysaccharide (LPS) and flagellin] on thiamin uptake and on transport of TPP
into their mitochondria. Thus, in new preliminary studies evidence were obtained to suggest that microRNAs
regulate THTR-1 expression and thiamin uptake by PACs, that THTR-1 has interacting partner(s), and that
exposure of PACs to pro-inflammatory cytokines (especially those implicated in pancreatic disorders like IL-
6, TNF-α and IL-1β), as well as to LPS and flagellin, inhibit cellular thiamin uptake and transport of TPP into
mitochondria. Based on these new findings, our working hypotheses are: i) microRNAs play an important role
in post-transcriptional regulation of THTR-1, THTR-2, and MTPPT expression in PACs and the uptake events
they mediate; ii) PACs THTR-1 and THTR-2 have interacting partners that affect/regulate their physiology/cell
biology; and iii) pro- inflammatory cytokines, LPS and flagellin negatively impact PACs thiamin transport
physiology. We plan to test these hypotheses by accomplishing two specific aims and will utilize state-of the
art cellular/molecular approaches, human and mouse PACs, and appropriate transgenic mouse models. Results
of these investigations should provide novel information regarding vitamin B1 cellular/molecular transport
physiology in PACs and how internal/external factors affect the involved transport event...

## Key facts

- **NIH application ID:** 9895584
- **Project number:** 5R01AA018071-12
- **Recipient organization:** SOUTHERN CALIFORNIA INST FOR RES/EDUC
- **Principal Investigator:** HAMID M SAID
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492,764
- **Award type:** 5
- **Project period:** 2009-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895584

## Citation

> US National Institutes of Health, RePORTER application 9895584, Physiology/Pathophysiology of Vitamin B1 Transport in Pancreatic Acinar Cells (5R01AA018071-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895584. Licensed CC0.

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