# Effect of Arestin Domain-Containing 4 Protein on Glucose Metabolism

> **NIH NIH F32** · HARVARD UNIVERSITY · 2024 · $86,932

## Abstract

Project Summary
The Arrestin superfamily of proteins controls the trafficking, turnover and signaling of trans-
membrane receptors, as well as other intracellular signaling functions. Several members of the
family, including ARRDC3 and TXNIP, are now known to have important roles in metabolism.
ARRDC4 is an understudied protein that has been shown to inhibit glucose uptake in vitro,
interact with ubiquitin ligases and plays a role in membrane receptor trafficking. The in vivo
functions and the molecular mechanisms of ARRDC4 are unknown. My preliminary experiments
reveal that mice with systemic deletion of ARRDC4 are glucagon resistant compared to wildtype
controls. Decreased hepatic gluconeogenesis and glucagon signaling and defects in hepatic
glucose production suppression were also observed in the liver tissues of ARRDC4KO mice. I
have now generated a new conditional deletion ARRDC4 mouse model for this project.
The glucagon receptor is a GPCR, and therefore a potential target to interact with arrestin family
proteins. As ARRDC4 interacts with membrane proteins and 7TM receptors, an important goal
of my research is to answer if ARRDC4 controls glucagon signaling by interacting with glucagon
receptors or its downstream mediators. The specific aims of this project will focus on unraveling
the functions of ARRDC4 in hepatic glucose metabolism in vivo and the mechanism of ARRDC4
regulation at the molecular level. Because ARRDC4 is itself regulated by glucose and insulin,
defining the metabolic functions of ARRDC4 has the potential to reveal a metabolic feedback
loop in glucose metabolism that interfaces with glucagon signaling.

## Key facts

- **NIH application ID:** 10690720
- **Project number:** 5F32DK126289-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Sezin Dagdeviren
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $86,932
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-10-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690720

## Citation

> US National Institutes of Health, RePORTER application 10690720, Effect of Arestin Domain-Containing 4 Protein on Glucose Metabolism (5F32DK126289-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690720. Licensed CC0.

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