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Beta cell exhaustion and glucotoxicity in Diabetes

Award Number: R01DK123163
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: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Beta cell exhaustion and glucotoxicity in Diabetes - Project summary Diabetes is characterized by progressive loss or dysfunction of pancreatic insulin- producing β-cells. Previous efforts demonstrated loss of β-cell identity, rather than cell death, as a primary contributor in loss of functional β-cell mass in diabetes progression. Strikingly, this process is reversible, challenging the notion of permanent β-cell damage in diabetes. However, underlying mechanisms remain elusive, and we have poor understanding of the window for intervention to preserve or restore functional β-cell mass. The long-term goals of this project are to understand temporal progression and underlying mechanisms of loss of pancreatic β-cell identity in diabetes. In this proposal we seek to understand β-cell adaptation to metabolic changes and conditions, determine the temporal progression and underlying mechanisms of loss of β-cell mass and identity in diabetes in vivo, and ways to prevent or restore functional β-cell mass. Proposed studies will utilize novel inducible mouse models of monogenic neonatal diabetes and of polygenic type 2 diabetes to understand β-cell adaptation to changes in metabolism, determine the temporal progression and underlying mechanisms of loss of functional β- cell mass and identity in different forms of diabetes, the role of autophagy in this process, and mechanisms to mitigate glucotoxicity-induced β-cell failure. Successful completion of the proposed aims will provide new molecular and mechanistic insights into the adaptive potential of β-cells and will shed light on mechanisms to preserve β-cell mass and identity.


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 = $625,889 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	12/19/2025	NON-COMPETING CONTINUATION	$625,889
														Subtotal = $625,889

Issue Date FY: 2025 ( Subtotal = $616,559 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	12/24/2024	COMPETING CONTINUATION	$536,407
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	5/16/2025	COMPETING CONTINUATION	$80,152
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/23/2024	NON-COMPETING CONTINUATION	$0
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	4	5/29/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $616,559

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $393,750 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/28/2023	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2022 ( Subtotal = $393,750 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/5/2022	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2021 ( Subtotal = $393,750 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/29/2021	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2020 ( Subtotal = $393,750 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/23/2020	NEW	$393,750
														Subtotal = $393,750

Grand Total All Awards = $2,817,448

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Beta cell exhaustion and glucotoxicity in Diabetes

Award Number: R01DK123163

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: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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