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Dynamic PET imaging in skeletal muscle and adipose tissue to explore mechanisms of lower peripheral glucose uptake in African American Women

Award Number: R01DK112700
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary This is a competitive revision application to support the expansion of our funded project, R01 DK112700 “Dynamic PET imaging in skeletal muscle and adipose tissue to explore mechanisms of lower peripheral glucose uptake in African American Women.” (AAW) Our project was designed to expand our understanding of the metabolic differences responsible for the racial disparity (African American compared to Caucasian) in risk for diabetes. This competitive revision will allow us to expand the scope of our research protocol to include Hispanic women (HW). These studies are important because AAW and HW exhibit nearly a two-fold greater risk of developing type 2 diabetes (T2DM) compared to Caucasian women (CW). Reasons behind these racial disparities are not understood, but lower insulin sensitivity (IS), a major risk factor for development of T2DM, is observed in healthy, non-obese AA and H children and adults compared to matched Caucasians. Published data indicate an intrinsic physiologic difference in some aspect(s) of insulin- stimulated GU in peripheral tissues. The lower peripheral GU in AAW and HW could have potentially serious clinical consequences, as this may lead to a strain on the ß-cells due to the long term need for compensatory insulin secretion, resulting in greater risk for development of T2DM. The identification of specific tissues and biochemical pathways that underlie reduced insulin-stimulated GU would have important positive clinical relevance; that is that interventions that target the site of the decreased IS in lean AAW and HW could decrease subsequent IR in obese women, and thus lessen the risk for the development of T2DM. The specific aims of our current R01 address two hypotheses: 1) a lower rate of insulin- stimulated glucose transport underlies the reduction in insulin-stimulated GU in AAW; and 2) insulin-stimulated GU into adipose tissue is an important site of decreased insulin sensitivity in AAW. In addition, we will explore potential mechanisms responsible for these racial differences. With this expansion we will include studies in HW. In addition, a new aim will be included to explore additional mechanisms responsible for these racial differences. To assist with this new aim, we have engaged investigators from Emory University and Georgia Tech with extensive experience in liquid chromatography/ mass spectrometry (LC/MS) metabolomic and lipidomic analyses. Using, limited targeted metabolite analyses, we have shown that specific ceramides, diacylglycerols, and acylcarnitines are associated with insulin sensitivity in Caucasians. In summary, decreased peripheral GU in AAW and HW appears to be an early risk factor of T2DM. This will be the first study to demonstrate specific metabolic steps that are altered, the contribution of adipose tissue and skeletal muscle, and potential mechanisms underlying lower peripheral GU in AAW and HW. Our findings will provide insights into therapeutics that target mechanisms underlying lower peripheral GU specific to AAW and HW, which importantly may be implemented to decrease obesity-related insulin resistance and diabetes.


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: 2024 ( Subtotal = $0 )
2024	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/5/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/25/2022	NON-COMPETING CONTINUATION	$0
2022	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	7/7/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/28/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	7/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/15/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/26/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,442,440 )
2020	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	9/10/2020	SUPPLEMENT FOR EXPANSION	$709,588
2020	2020	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/22/2020	NON-COMPETING CONTINUATION	$732,852
														Subtotal = $1,442,440

Issue Date FY: 2019 ( Subtotal = $461,064 )
2019	2018	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/21/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2018	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	2	7/17/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2018	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	2	6/4/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$461,064
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	1	6/4/2019	NEW	-$461,064
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/9/2018	NEW	$0
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	6/3/2019	NEW	$461,064
														Subtotal = $461,064

Issue Date FY: 2018 ( Subtotal = $311,572 )
2018	2018	ADVENTIST HEALTH SYSTEM/SUNBELT, INC.	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	9/10/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$772,636
2018	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/7/2018	NEW	-$461,064
														Subtotal = $311,572

Issue Date FY: 2017 ( Subtotal = $661,931 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/28/2017	NEW	$661,931
														Subtotal = $661,931

Grand Total All Awards = $2,877,007

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Dynamic PET imaging in skeletal muscle and adipose tissue to explore mechanisms of lower peripheral glucose uptake in African American Women

Award Number: R01DK112700

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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