Summary of Study ST002204

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001407. The data can be accessed directly via it's Project DOI: 10.21228/M8V995 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002204
Study TitleEndothelial Sirtuin1 Suppresses Whole-body Insulin Sensitivity by Modulating the Secretome
Study TypeEnd point
Study SummarySirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4
Institute
University of Iowa
DepartmentInternal medicine
Laboratoryirani
Last NameIrani
First NameKaikobad
AddressRM 2256 CBRB, Newton Rd, Iowa City, IA 52242
Emailkaikobad-irani@uiowa.edu
Phone3193358821
Submit Date2021-12-02
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2022-07-22
Release Version1
Kaikobad Irani Kaikobad Irani
https://dx.doi.org/10.21228/M8V995
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003607
Analysis type MS
Chromatography type GC
Chromatography system Thermo Trace 1310
Column Thermo TraceGold TG-5SilMS
MS Type EI
MS instrument type Single quadrupole
MS instrument name Thermo ISQ
Ion Mode POSITIVE
Units AU
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