Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanisms for Impaired Adaptation to Aerobic Exercise with Metabolic Disease

Award Number: R01DK124258
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: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2030

Group Awards By:

View Award Description

Mechanisms for Impaired Adaptation to Aerobic Exercise with Metabolic Disease - PROJECT SUMMARY Low cardiorespiratory fitness (CRF) is one of the single strongest risk factors for disease and mortality. Aerobic exercise training is the only effective treatment to increase CRF and reduce the associated health risks. However, even when levels of physical activity are matched, CRF remains lower in people with metabolic diseases such as Type 1 and Type 2 diabetes compared to those without metabolic disease, suggesting impaired aerobic adaptation. The goal of this investigation is to determine the mechanisms that contribute to low aerobic adaptation in metabolic disease, and develop treatment strategies to improve the response to exercise. Clinical studies indicate that persistently low CRF in those with diabetes is linked to chronically high blood glucose levels (i.e., hyperglycemia). Aerobic remodeling of skeletal muscles toward a more oxidative fiber type and higher capillary density contributes to improved CRF with exercise training. Our work indicates that aerobic remodeling of muscle is blunted by chronic hyperglycemia and may be a cause for the failure to improve CRF in people with diabetes. We have identified two mechanisms that may contribute to impaired aerobic remodeling of muscle with hyperglycemia: 1) Muscle extracellular matrix accumulation, and 2) Altered muscle signaling with exercise via the JNK/SMAD2 pathway. Our central hypothesis is that chronic hyperglycemia induces extracellular matrix accumulation in muscle and alters mechanical signaling via JNK/SMAD2, impairing aerobic remodeling and impeding improvements in CRF. We will test this hypothesis using a multi-faceted approach employing serum from human participants, tissue culture systems, and genetically modified mouse models. Our research plan will determine how chronic hyperglycemia alters muscle extracellular matrix production and mechanical properties. We will also identify whether JNK/SMAD2 signaling is a therapeutic target to restore aerobic adaptation in models of hyperglycemia. This project will significantly advance our understanding of the mechanisms that cause low aerobic adaptation in people with metabolic disease, and identify treatments to improve CRF, health span, and longevity.


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 = $709,867 )
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	2/18/2026	COMPETING CONTINUATION	$709,867
2026	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/11/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $709,867

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $475,718 )
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	9/10/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$475,718
2024	2023	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $475,718

Issue Date FY: 2023 ( Subtotal = $528,727 )
2023	2023	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/2/2023	NON-COMPETING CONTINUATION	$528,727
														Subtotal = $528,727

Issue Date FY: 2022 ( Subtotal = $528,727 )
2022	2022	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/10/2022	NON-COMPETING CONTINUATION	$528,727
														Subtotal = $528,727

Issue Date FY: 2021 ( Subtotal = $550,129 )
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/9/2021	NON-COMPETING CONTINUATION	$550,129
														Subtotal = $550,129

Issue Date FY: 2020 ( Subtotal = $549,519 )
2020	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/11/2020	NEW	$549,519
														Subtotal = $549,519

Grand Total All Awards = $3,342,687

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms for Impaired Adaptation to Aerobic Exercise with Metabolic Disease

Award Number: R01DK124258

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: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer