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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)
PERIOD OF PERFORMANCE START DATE: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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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 - African-American women (AAW) exhibit more than a two-fold greater risk of developing type 2 diabetes (T2DM) compared to Caucasian women (CW). Reasons behind this racial disparity are not understood, but lower insulin sensitivity (IS), a major risk factor for development of T2DM, is observed in lean, overweight and obese AAW compared to matched CW. We recently demonstrated a 26% lower IS in young, healthy, non- obese AAW compared to matched CW. Specifically, this difference was due exclusively to lower peripheral glucose uptake (GU), which occurs primarily in skeletal muscle, but also in adipose tissue, with the liver showing comparable IS. The lower peripheral GU could have potentially serious clinical consequences for AAW as this may lead to a strain on the β-cells due to the long term need for compensatory insulin secretion, resulting in greater risk for development of T2DM. The identification of specific tissue and biochemical pathways that underlie reduced insulin-stimulated GU in AAW would have important positive clinical relevance; that is, interventions that target the specific mechanism(s) of the decreased GU in lean AAW could decrease subsequent IR in obese AAW, and thus lessen the risk for the development of T2DM. Our specific aims will 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. Furthermore, we will explore whether racial differences in skeletal muscle (e.g. fiber type, levels of Glut4 and Hexokinase) and adipokines (e.g. Adiponectin and RBP4), are associated with racial differences in GU. Aim 1. To examine the specific steps of GU responsible for the reduced insulin stimulated peripheral GU in non-obese AAW compared to CW. We will perform dynamic PET imaging during a hyperinsulinemic euglycemic clamp and apply kinetic modeling to quantify in vivo rates of glucose delivery, transport and phosphorylation within skeletal muscle and adipose tissue, and how control of GU is distributed between these steps. Glucose transport is the major control step for insulin-stimulated GU, but glucose delivery and phosphorylation are also involved. We focus this study in non-obese women to better understand in vivo factors that contribute to the lower insulin-stimulated GU we recently observed in non-obese AAW compared to CW. We expect that lower glucose transport is the primary mechanism underlying the lower GU in AAW. Aim 2. To characterize the contribution of skeletal muscle (biceps femoris and vastus lateralis) and adipose tissue (visceral, abdominal and mid-thigh subcutaneous) to the lower insulin stimulated GU in AAW compared to CW. In addition to mid-thigh PET imaging described in Aim 1, we will also perform abdominal imaging to measure overall GU in different skeletal muscles and adipose tissues. We will also perform a muscle biopsy to measure the proportion of Type I fibers, and levels of GLUT4 and hexokinase in vastus lateralis. In addition, we will measure plasma levels of adipokines secreted by adipose tissue.


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 = $0 )
2025	2020	ADVENTIST HEALTH SYSTEM/SUNBELT INC	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

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	002	3	7/7/2022	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	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	001	2	6/28/2022	SUPPLEMENT FOR EXPANSION	$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	000	2	11/26/2020	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	001	2	6/15/2021	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	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	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	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)

PERIOD OF PERFORMANCE START DATE: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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