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Effect of Arestin Domain-Containing 4 Protein on Glucose Metabolism

Award Number: F32DK126289
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 10/28/2024

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$2,289 )
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	9/25/2025	NON-COMPETING CONTINUATION	-$2,289
														Subtotal = -$2,289

Issue Date FY: 2024 ( Subtotal = $86,932 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/9/2024	NON-COMPETING CONTINUATION	$6,004
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	10/27/2023	NON-COMPETING CONTINUATION	$80,928
														Subtotal = $86,932

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $76,442 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/25/2022	NON-COMPETING CONTINUATION	$76,442
														Subtotal = $76,442

Issue Date FY: 2021 ( Subtotal = $70,458 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/26/2021	NEW	$0
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/26/2021	NEW	$70,458
														Subtotal = $70,458

Grand Total All Awards = $231,543

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Effect of Arestin Domain-Containing 4 Protein on Glucose Metabolism

Award Number: F32DK126289

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 10/28/2024

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