# The Role of Arginine Transport on Pancreatic Alpha Cell Proliferation and Function

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $31,741

## Abstract

Project Summary
 The training strategy demonstrated in this document will help me advance my career to be an
independent research scientist in the field of diabetes. I propose to assess the role of arginine transport in the
regulation of pancreatic islet cell proliferation and hormone secretion. Disease progression of diabetes is
attributed to the inability of pancreatic β-cells to sufficiently secrete insulin and the combined failure to suppress
pancreatic α-cell secretion of glucagon. Inhibition of glucagon signaling reduces hyperglycemia for individuals
with diabetes.3 However, impairment of glucagon signaling leads to hyperglucagonemia, hyperaminoacidemia,
and α-cell proliferation.4,5 Our lab has identified a liver-α-cell axis that contributes to α-cell proliferation through
the accumulation of amino acids in the blood.4 We have identified two major amino acids that contribute to α-cell
proliferation, glutamine4 and arginine (unpublished data). However, the mechanisms underlying arginine
transport in the α-cell specifically and its contribution to α-cell proliferation and secretion are not well defined.
The cationic amino acid transporter SLC7A2 is highly expressed in mouse and human pancreatic α-cells.
Therefore, we hypothesize that hyperaminoacidemia that results from interrupted glucagon signaling
contributes to increased arginine transport promoting α-cell proliferation and dysfunction. Our
preliminary studies show that SLC7A2 is required for α-cell proliferation and glucagon secretion even when
challenged with strong membrane depolarizing agents challenging current cation-centric models of arginine
stimulated secretion (Figure 2 and 4). Using a new α-cell specific Slc7a2 knockout mouse model, we will unravel
the molecular mechanisms that lead to arginine-stimulated α-cell proliferation and glucagon secretion. To assess
whether SLC7A2 in α-cells is necessary for amino acid-dependent α-cell proliferation, Slc7a2 knockout in
immortalized mouse αTC1-6 cells and an inducible α-cell specific Slc7a2 knockout mouse model will be used to
assess changes in α-cell proliferation and mass. Additionally, the mechanism of arginine-induced mTORC1
activation will be targeted to determine if arginine activates mTORC1 through the inactivation of the CASTOR1-
GATOR2 pathway (Aim 1). Furthermore, to test the ability for arginine transport via SLC7A2 to modulate
glucagon secretion we will combine tools used in Aim 1 with chemical and genetically encoded Ca2+ sensors to
observe changes in α-cell glucagon secretion. We will also measure nitric oxide levels, and test the affect of
nitric oxide on glucagon secretion to understand the mechanism behind arginine-induced glucagon secretion
(Aim 2). Successfully accomplishing this study will enhance our current understanding of amino acid-induced α-
cell proliferation and function, as well as broaden the possibilities of therapeutic treatments for diabetes. My
training will be achieved through the execution of this st...

## Key facts

- **NIH application ID:** 10852835
- **Project number:** 5F31DK134158-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jade Elise Stanley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $31,741
- **Award type:** 5
- **Project period:** 2023-06-01 → 2025-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852835

## Citation

> US National Institutes of Health, RePORTER application 10852835, The Role of Arginine Transport on Pancreatic Alpha Cell Proliferation and Function (5F31DK134158-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852835. Licensed CC0.

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