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Identification of diabetes susceptibility genes via an integrated functional genomics analysis of gene-diet interaction

Award Number: R15DK113604
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 The global prevalence of Type 2 diabetes (T2D) is a major health concern. There is strong evidence of a genetic basis for human T2D, which follows a polygenic pattern of inheritance. Epidemiological and experimental data suggest that T2D arises from the interplay between genetics and environment (e.g., diet), partly explaining the current diabetes epidemic in a Western environment of excessive energy- dense food consumption. Despite this evidence, the exact nature of gene-diet interactions and underlying causal mechanisms are poorly understood in T2D. One major reason originates from difficulties in accurate dietary assessment in humans, partly due to unreliable methodology such as dietary recalls and questionnaires and individual's subjective perception about food intake. One approach to address this complexity is to use animal models, where the environment can be carefully controlled and modified. TALLYHO (TH) mice encompass many aspects of polygenic human T2D. Our preliminary studies demonstrated that the penetrance of genetic susceptibility to T2D is modulated in TH mice by nutritionally modified diets. Therefore, we hypothesize that (1) the susceptibility of TH mice to T2D is modulated by the combined interaction of diet and genetics which act to alter gene expression in selected tissues and (2) identification of genes whose expression varies with this interaction will enable us to identify T2D susceptibility genetic variants in the TH mouse. To test these hypotheses we will: (1) investigate chronological development of insulin resistance and impairment of insulin secretion in response to diabetogenic diets in TH mice and (2) characterize global gene expression changes caused by diabetogenic diets in TH vs. B6 and F1(FVBxB6) mice and identify the associated genetic variants and pathways by using an integrated functional genomics approach. These studies will identify molecular predictors that connect diet with the etiology of T2D. !


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 = -$12,194 )
2024	2018	MARSHALL UNIVERSITY RESEARCH CORPORATION	1 JOHN MARSHALL DR	HUNTINGTON	WV	25755	CABELL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	10/1/2023	NEW	-$12,194
														Subtotal = -$12,194

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	MARSHALL UNIVERSITY RESEARCH CORPORATION	ONE JOHN MARSHALL DRIVE	HUNTINGTON	WV	25755	CABELL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/9/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $440,405 )
2018	2018	MARSHALL UNIVERSITY RESEARCH CORPORATION	ONE JOHN MARSHALL DRIVE	HUNTINGTON	WV	25755	CABELL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/7/2018	NEW	$440,405
														Subtotal = $440,405

Grand Total All Awards = $428,211

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Identification of diabetes susceptibility genes via an integrated functional genomics analysis of gene-diet interaction

Award Number: R15DK113604

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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