Sunday, August 3, 2025 8/3/2025

MECHANISM REGULATING EXPRESSION OF THE UCP2 GENE

Award Number: R01DK054024
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: 07/15/1998
PERIOD OF PERFORMANCE END DATE: 02/28/2006

Group Awards By:

View Award Description

MECHANISM REGULATING EXPRESSION OF THE UCP2 GENE - DESCRIPTION (provided by applicant): Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by a defect in glucose-stimulated insulin secretion from pancreatic beta-cells that can lead to frank diabetes. Intensive searches for the mechanisms underlying this progressive failure of beta-cells suggest a role for free fatty acids (FFAs). In 1997, in collaboration with Daniel Ricquier, we reported the discovery of uncoupling protein 2 (UCP2), a homologue of the brown fat UCP with genetic linkage to hyperinsulinemia. We propose that there is an important link between areas of investigation, which may provide insight into the regulation of metabolic fuel usage and regulation of insulin secretion. First, many studies have linked the regulation of Ucp2 expression in adipose and muscle tissues to changes in energy metabolism, particularly the level of free fatty acids (FFAs). Second, FFAs are known to modulate glucose-stimulated insulin secretion. Third, several lines of evidence, including preliminary studies presented in this application, support the conclusion that changes in UCP2 expression in pancreatic beta-cells can affect the sensitivity to glucose for stimulation of insulin secretion. Our two main objectives for this new project period are as follow: First to characterize the metabolic disturbances of pancreatic beta-cells from our Ucp2-/-mice, and define the role of Ucp2 in insulin secretion. Using the Ucp2-/- mouse model, we will test the hypothesis that the loss in glucose-stimulated insulin secretion following chronic exposure to FFAs is due to increased expression of UCP2 in beta-cells. Second, we propose to investigate the mechanisms of transcriptional regulation of the Ucp2 gene in pancreatic beta-cells. During the previous 3-yr project period we characterized the mouse Ucp2 promoter and identified an enhancer region (86/-44) composed of Sp 1, SRE and double E-box motifs. This region is required for basal and PPAR-induced expression of the Ucp2 gene in adipose cells. The PPAR-response is mediated by the double E-boxes. In this new project period we will use the INS-1 beta-cell subclone, 1NS(832/13), as well as transgenic mice expressing UCP2 promoter reporter constructs to test the hypothesis that FFAs and/or glucose regulate UCP2 expression through the proximal tripartite enhancer region, and we will identify the trans-activating factors implicated in its regulation through classical transfection and gel shift approaches. These studies will characterize the interplay between FFAs and glucose on control of UCP2 expression at the molecular level as well as the consequence of UCP2 modulation on insulin secretion.


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: 2005 ( Subtotal = $321,493 )
2005	2005	CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY	POST OFFICE BOX 12137	RESCH TRIANGLE PK	NC	27709		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	2/21/2005	NON-COMPETING CONTINUATION	$321,493
														Subtotal = $321,493

Issue Date FY: 2004 ( Subtotal = $319,272 )
2004	2004	CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY	POST OFFICE BOX 12137	RESCH TRIANGLE PK	NC	27709		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	9/6/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$295,012
2004	2004	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	2/19/2004	NON-COMPETING CONTINUATION	$24,260
														Subtotal = $319,272

Issue Date FY: 2003 ( Subtotal = $294,527 )
2003	2003	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5		NON-COMPETING CONTINUATION	$294,527
														Subtotal = $294,527

Issue Date FY: 2002 ( Subtotal = $336,105 )
2002	2002	DUKE UNIVERSITY	POST OFFICE BOX 40005	DURHAM	NC	27706	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/12/2002	COMPETING CONTINUATION	$336,105
														Subtotal = $336,105

Issue Date FY: 2000 ( Subtotal = $176,407 )
2000	2000	Duke University	OFFICE OF SPONSORED PROGRAMS	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/1/2000	NON-COMPETING CONTINUATION	$176,407
														Subtotal = $176,407

Issue Date FY: 1999 ( Subtotal = $185,271 )
1999	1999	Duke University	OFFICE OF SPONSORED PROGRAMS	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/23/1999	NON-COMPETING CONTINUATION	$185,271
														Subtotal = $185,271

Issue Date FY: 1998 ( Subtotal = $173,216 )
1998	1998	Duke University	OFFICE OF SPONSORED PROGRAMS	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/8/1998	NEW	$173,216
														Subtotal = $173,216

Grand Total All Awards = $1,806,291

Top

All Categories

About

Search

Reports

Data Submission

Award Information

MECHANISM REGULATING EXPRESSION OF THE UCP2 GENE

Award Number: R01DK054024

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: 07/15/1998

PERIOD OF PERFORMANCE END DATE: 02/28/2006

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer