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Restoring Central Regulation of Glucose Production in Type 2 Diabetes

Award Number: R01DK069861
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: 06/15/2006
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Restoring Central Regulation of Glucose Production in Type 2 Diabetes - Project Summary/Abstract Endogenous glucose production (EGP) is a crucial process that maintains blood glucose levels under fasting conditions and is normally inhibited by both glucose and insulin. Inappropriately high EGP is the major source of hyperglycemia in individuals with type 2 diabetes (T2D) and contributes significantly to diabetes complications. Our groups’ ongoing work suggests that central nervous system (CNS) signals play an important role in regulating EGP. ATP-sensitive potassium (KATP) channels in the ventromedial hypothalamus (VMH) appear to mediate some of the suppressive effects of circulating insulin and glucose on EGP, but this regulation is impaired in T2D and diabetic rodents. We have observed that lowering free fatty acid (FFA) levels completely restored the regulation of EGP by central KATP channel activation. Therefore, we hypothesize that chronic lipid overload may contribute to the central signaling defects in T2D. Thus, through complementary human and rodent studies we propose to expand our understanding of how specific CNS signaling pathways regulate EGP through the following specific aims: 1) To establish whether central regulation of EGP can be restored by lowering FFA levels in patients with T2D, 2) To determine whether intact hepatic innervation is required for restoration of central regulation of EGP upon lowering FFA in individuals with T2D, and 3) To establish whether the impaired central regulation of EGP in T2D is mediated by neuron-specific defects in KATP channel activation within the VMH. Furthermore, we will determine whether lowering FFA levels contributes to restoring central regulation of glucose production by reducing endoplasmic reticulum (ER) stress in specific glucose-sensing neurons. Collectively, these studies should provide mechanistic explanation(s) for the impaired central regulation of EGP in T2D and help point toward novel therapeutic targets.


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 = $677,112 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	5/9/2025	NON-COMPETING CONTINUATION	$677,112
2025	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	4/29/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $677,112

Issue Date FY: 2024 ( Subtotal = $789,963 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	14	5/14/2024	SUPPLEMENT FOR EXPANSION	$125,335
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	5/13/2024	NON-COMPETING CONTINUATION	$664,628
														Subtotal = $789,963

Issue Date FY: 2023 ( Subtotal = $793,258 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	6/1/2023	NON-COMPETING CONTINUATION	$699,257
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	8/21/2023	SUPPLEMENT FOR EXPANSION	$94,001
														Subtotal = $793,258

Issue Date FY: 2022 ( Subtotal = $705,944 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	6/23/2022	NON-COMPETING CONTINUATION	$705,944
														Subtotal = $705,944

Issue Date FY: 2021 ( Subtotal = $729,169 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	4/22/2021	COMPETING CONTINUATION	$729,169
														Subtotal = $729,169

Issue Date FY: 2020 ( Subtotal = -$116 )
2020	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	2/3/2020	NON-COMPETING CONTINUATION	-$116
														Subtotal = -$116

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	12/13/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $553,838 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	10	6/22/2016	NON-COMPETING CONTINUATION	$553,838
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	10/23/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$510,604
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	10/23/2015	NON-COMPETING CONTINUATION	-$510,604
														Subtotal = $553,838

Issue Date FY: 2015 ( Subtotal = $557,023 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	7/28/2015	NON-COMPETING CONTINUATION	$557,023
														Subtotal = $557,023

Issue Date FY: 2014 ( Subtotal = $560,206 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	7/15/2014	NON-COMPETING CONTINUATION	$560,206
														Subtotal = $560,206

Issue Date FY: 2013 ( Subtotal = $563,391 )
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	7/17/2013	COMPETING CONTINUATION	$563,391
														Subtotal = $563,391

Issue Date FY: 2010 ( Subtotal = $320,584 )
2010	2010	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/28/2010	NON-COMPETING CONTINUATION	$320,584
														Subtotal = $320,584

Issue Date FY: 2009 ( Subtotal = $323,823 )
2009	2009	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/26/2009	NON-COMPETING CONTINUATION	$323,823
														Subtotal = $323,823

Issue Date FY: 2008 ( Subtotal = $323,823 )
2008	2008	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/2/2008	NON-COMPETING CONTINUATION	$323,823
														Subtotal = $323,823

Issue Date FY: 2007 ( Subtotal = $330,431 )
2007	2007	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/21/2007	NON-COMPETING CONTINUATION	$330,431
														Subtotal = $330,431

Issue Date FY: 2006 ( Subtotal = $340,129 )
2006	2006	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/12/2006	NEW	$340,129
														Subtotal = $340,129

Grand Total All Awards = $7,568,578

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Restoring Central Regulation of Glucose Production in Type 2 Diabetes

Award Number: R01DK069861

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: 06/15/2006

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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