Friday, March 20, 2026 3/20/2026

Role of CREG1 in metabolic homeostasis

Award Number: R01DK135309
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/16/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Role of CREG1 in metabolic homeostasis - Project Summary Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and reduced insulin secretion. Cellular repressor of E1A-stimulated genes 1 (CREG1), a small glycoprotein involved in membrane trafficking in the endocytic and secretory pathways, may be involved in the pathogenesis of T2DM, as suggested by the insulin resistance, glucose intolerance, elevated glycemia and hypoinsulinemia in whole-body Creg1 knockout mice. Gain- and loss-of-function studies using cultured hepatocytes and liver-specific Creg1 knockout mice demonstrate that CREG1 autonomously regulates cellular insulin signaling, insulin sensitivity, and the expression of insulin receptor on the plasma membrane. In pancreatic ?-cell-specific Creg1 knockout islets, increased proinsulin and diminished insulin levels lead to impaired insulin secretion. Furthermore, CREG1 expression is nutritionally regulated and is progressively downregulated by high-fat diet consumption. This project will test (1) whether loss of CREG1 inhibits insulin receptor recycling and consequently impairs insulin signaling and insulin action, (2) to what degree CREG1 downregulation contributes to insulin resistance in metabolic disease, and (3) whether Creg1 ablation impedes insulin granule trafficking and enhances insulin degradation. In the first Aim, we will delineate the role of CREG1 in the regulation of insulin receptor trafficking and its contribution to hepatic insulin action and cellular insulin signaling. We will restore CREG1 expression in high fat diet fed mice via adeno- associated virus-mediated CREG1 gene delivery and test if this improves insulin sensitivity and insulin signaling. In the second Aim, we will elucidate how loss of CREG1 leads to reduced ?-cell insulin content with a focus on proinsulin processing and insulin degradation. Pulse-chase labeling and live cell imaging, electron microscopy, and biochemical analysis combined with complex physiological study protocols will be used in the proposed studies. Our long-term goals are to elucidate how CREG1 regulates hepatic insulin action and ?-cell insulin secretion, and to target CREG1 to treat T2DM.


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: 2026 ( Subtotal = $492,547 )
2026	2026	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/30/2026	NON-COMPETING CONTINUATION	$492,547
														Subtotal = $492,547

Issue Date FY: 2025 ( Subtotal = $443,293 )
2025	2025	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/25/2025	NON-COMPETING CONTINUATION	$443,293
														Subtotal = $443,293

Issue Date FY: 2024 ( Subtotal = $472,845 )
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/17/2024	NON-COMPETING CONTINUATION	$29,552
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/5/2024	NON-COMPETING CONTINUATION	$443,293
														Subtotal = $472,845

Issue Date FY: 2023 ( Subtotal = $492,547 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/16/2023	NEW	$492,547
														Subtotal = $492,547

Grand Total All Awards = $1,901,232

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of CREG1 in metabolic homeostasis

Award Number: R01DK135309

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/16/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer