PXD043032

PXD043032 is an original dataset announced via ProteomeXchange.

Title	Nonequilibrium Thermodynamics and Mitochondrial Protein Content Predict Insulin Sensitivity and Fuel Selection During Exercise in Human Skeletal Muscle
Description	Introduction. Many investigators have attempted to define the molecular nature of changes responsible for insulin resistance in muscle, but a molecular approach may not consider the overall physiological context of muscle. Because the energetic state of ATP (ΔGATP) could affect the rate of insulin-stimulated, energy-consuming processes, the present study was undertaken to determine whether the thermodynamic state of skeletal muscle can partially explain insulin sensitivity and fuel selection independently of molecular changes. Methods. 31P-MRS was used with glucose clamps, exercise studies, muscle biopsies and proteomics to measure insulin sensitivity, thermodynamic variables, mitochondrial protein content, and aerobic capacity in 16 volunteers. Results. After showing calibrated 31P-MRS measurements conformed to a linear electrical circuit model of muscle nonequilibrium thermodynamics, we used these measurements in multiple stepwise regression against rates of insulin-stimulated glucose disposal and fuel oxidation. Multiple linear regression analyses showed 53% of the variance in insulin sensitivity was explained by 1) VO2max (P = 0.001) and the 2) slope of the relationship of GATP with the rate of oxidative phosphorylation (P = 0.007). This slope represents conductance in the linear model (functional content of mitochondria). Mitochondrial protein content from proteomics was an independent predictor of fractional fat oxidation during mild exercise (R2 = 0.55, P = 0.001). Conclusions. Higher mitochondrial functional content is related to the ability of skeletal muscle to maintain a greater GATP, which may lead to faster rates of insulin-stimulated processes. Mitochondrial protein content per se can explain fractional fat oxidation during mild exercise.
HostingRepository	PRIDE
AnnounceDate	2023-06-29
AnnouncementXML	Submission_2023-06-29_11:10:12.883.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043032
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	PaulLanglais
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-15 13:22:30	ID requested
⏵ 1	2023-06-29 11:10:13	announced

10.6019/PXD043032;

submitter keyword: 31P-Magnetic Resonance Spectroscopy, Exercise, Mitochondria,Skeletal Muscle, Insulin Sensitivity, Fuel Selection

LawrenceMandarino
contact affiliation	University of Arizona College of Medicine-Tucson, Department of Medicine, Division of Endocrinology
contact email	mandarino@arizona.edu
lab head
PaulLanglais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043032
     1. Label: PRIDE project
     2. Name: Nonequilibrium Thermodynamics and Mitochondrial Protein Content Predict Insulin Sensitivity and Fuel Selection During Exercise in Human Skeletal Muscle