Material Type  

 학위논문

 

0016931846

Date and Time of Latest Transaction  

20240214100126

ISBN  

9798379755874

DDC  

574

Author  

Blair, Megan C.

Title/Author  

Branched-Chain Amino Acid Catabolism in Skeletal Muscle Controls Systemic BCAA Levels Without Impacting Insulin Resistance - [electronic resource]

Publish Info  

[S.l.] : University of Pennsylvania., 2023

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Material Info  

1 online resource(114 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

General Note  

Advisor: Arany, Zoltan Pierre;Wellen, Kathryn E.

학위논문주기  

Thesis (Ph.D.)--University of Pennsylvania, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Abstracts/Etc  

요약Elevated plasma branched-chain amino acids (BCAAs) have been associated with type 2 diabetes since the 1960s. Pharmacological activation of branched-chain α-ketoacid dehydrogenase (BCKDH), the rate-limiting enzyme of BCAA oxidation, lowers plasma BCAAs and improves glucose tolerance in both rodents and humans. However, how BCAA oxidation alleviates insulin resistance, and through which tissues, remains unclear. To address these questions, we developed skeletal muscle and liver-specific BCKDH gain-of-function and loss-of-function mouse models, and comprehensively evaluated glucose homeostasis. We found that altered BCAA oxidation in neither skeletal muscle nor liver, alone or in combination, is sufficient to improve or worsen insulin sensitivity in male mice fed chow or high-fat diet. Modulation of BCKDH activity in skeletal muscle, but not liver, affected fasting plasma BCAAs. However, despite lowering systemic BCAA levels, skeletal muscle-specific increase in BCAA oxidation did not improve insulin sensitivity. These data show that skeletal muscle controls plasma BCAAs, that lowering fasting plasma BCAAs is insufficient to improve insulin sensitivity, and that neither skeletal muscle nor liver account for the improved insulin sensitivity seen with pharmacological activation of BCKDH. Our findings suggest concerted contributions of multiple tissues in the modulation of BCAA metabolism to alter insulin sensitivity.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Physiology.

Index Term-Uncontrolled  

Amino acid catabolism

Index Term-Uncontrolled  

BCAA oxidation

Index Term-Uncontrolled  

Insulin resistance

Index Term-Uncontrolled  

Pharmacological activation

Added Entry-Corporate Name  

University of Pennsylvania Cell and Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 85-01B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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소장사항  

202402 2024

Control Number  

joongbu:639726