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Parsing the central control of thirst and hunger using a rat model of diabetes insipidus

Award Number: R01DK133818
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: 08/17/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Parsing the central control of thirst and hunger using a rat model of diabetes insipidus - Project Summary: Feeding and drinking are essential behaviors for the maintenance of energy and fluid homeostasis. Failure to maintain energy balance causes obesity or malnutrition and perturbations in fluid balance cause dehydration or hypertension. The neural circuits that control hunger and thirst have been well studied but overlapping neural pathways in the control of hunger or of thirst, and the strong interdependence of feeding and drinking has made it difficult to untangle the respective circuits. To address this long-standing problem, this project takes a novel approach that uses the Brattleboro rat to tease apart aspects of the glucagon-like peptide-1 (GLP-1) system that control feeding and drinking. The Brattleboro rat is a well-studied rodent model of central diabetes insipidus that originated in a colony of Long Evans rats. A naturally occurring single nucleotide mutation in these rats results in a vasopressin precursor that cannot be secreted, causing severe polyuria. To compensate for the polyuria, Brattleboro rats drink approximately five times that consumed by wild-type littermates, without any observed feeding-related phenotype. A series of studies in our laboratory suggest that at least part of the polydipsia involves disrupted satiety signals. Specifically, licking microstructure analyses revealed differences that are consistent with altered satiation and additional studies suggest that Brattleboro rats have altered fluid intake-relevant GLP-1 signaling, but intact feeding-related GLP-1 responses. Moreover, Brattleboro rats appear to have different GLP-1 precursor expression in the hindbrain when compared with that of wild type littermates. Taking advantage of these differences in fluid intake, in the absence of differences in food intake, this project uses a variety of approaches to better elucidate circuits responsible for the control of drinking, especially relevant for satiation of thirst, and to separate these from circuits responsible for food intake. Accordingly, by testing for differences between wild-type and Brattleboro rats, we can identify circuits and populations of cells in the GLP-1 system that control drinking and separate them from those that control other functions such as feeding. As such, these data will lead to a more complete understanding of the circuits that control fluid and food intake satiety and provide targets for treatments of disordered energy and fluid homeostasis.


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 = $537,476 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/8/2025	NON-COMPETING CONTINUATION	$537,476
														Subtotal = $537,476

Issue Date FY: 2024 ( Subtotal = $521,803 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/12/2024	NON-COMPETING CONTINUATION	$521,803
														Subtotal = $521,803

Issue Date FY: 2023 ( Subtotal = $535,735 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/5/2023	NON-COMPETING CONTINUATION	$535,735
														Subtotal = $535,735

Issue Date FY: 2022 ( Subtotal = $500,478 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/15/2022	NEW	$500,478
														Subtotal = $500,478

Grand Total All Awards = $2,095,492

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Parsing the central control of thirst and hunger using a rat model of diabetes insipidus

Award Number: R01DK133818

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: 08/17/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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