Summary of Study ST002204

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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
University of Iowa
DepartmentInternal medicine
Last NameIrani
First NameKaikobad
AddressRM 2256 CBRB, Newton Rd, Iowa City, IA 52242
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 application/zip

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Project ID:PR001407
Project DOI:doi: 10.21228/M8V995
Project Title:Endothelial Sirtuin1 Suppresses Whole-body Insulin Sensitivity by Modulating the Secretome
Project Type:Profiling metabolites in skeletal muscle
Project Summary:Profiling metabolites in skeletal muscle from wild type vs. endothelium-specific Sirt1 knockout (E-Sirt1-KO) mice.
Institute:University of Iowa
Department:Internal medicine
Laboratory:Irani lab
Last Name:Irani
First Name:Kaikobad
Address:RM 2256 CBRB, Newton Rd, Iowa City, IA 52242
Funding Source:AHA Award #20CDA35320042


Subject ID:SU002290
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:wild type and endothelium-specific Sirt1 knockout mice
Age Or Age Range:12 weeks old
Weight Or Weight Range:~30 g
Height Or Height Range:n/a
Animal Animal Supplier:Jax
Animal Housing:University of Iowa animal house
Animal Light Cycle:12 h light/12 h night
Animal Feed:Standard Chow
Animal Water:Tap water
Animal Inclusion Criteria:n/a
Species Group:n/a


Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
Showing results 1 to 9 of 9


Collection ID:CO002283
Collection Summary:40 mg of tibialis anterior was rapidly harvested and frozen immediately in liquid nitrogen. Metabolites were separated, measured, and analyzed.
Sample Type:Muscle


Treatment ID:TR002302
Treatment Summary:After 5 to 6 h of fasting, mice were anesthetized and skeletal muscle were collected.

Sample Preparation:

Sampleprep ID:SP002296
Sampleprep Summary:Tissue samples were lyophilized overnight prior to bead mill homogenization in 18:1 (µl:mg wet tissue weight) ice-cold 2:2:1 methanol:acetonitrile:water extraction buffer containing a mixture of internal standards (D4-citric acid, D4-succinic acid, D8-valine, and U13C-labeled glutamine, glutamic acid, lysine, methionine, serine, and tryptophan; Cambridge Isotope Laboratories). Homogenates were rotated for 1 hour at -20°C. Homogenates were centrifuged for 10 minutes at 21,000 x g, and 150 µl of the cleared metabolite extracts were transferred to autosampler vials and dried using a SpeedVac vacuum concentrator (Thermo). Dried metabolite extracts were reconstituted in 30 μl of 11.4 mg/ml methoxyamine (MOX) in anhydrous pyridine, vortexed for 5 minutes, and heated for 1 hour at 60°C. Next, to each sample 20 μl of N,O-Bis(trimethylsilyl)trifluoroacetamide (TMS) was added, samples were vortexed for 1 minute, and heated for 30 minutes at 60°C.
Sampleprep Protocol Filename:GC_Method_Tissue.pdf

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
Units AU


Chromatography ID:CH002666
Chromatography Summary:1 μl of derivatized sample was injected into a Trace 1300 GC (Thermo) fitted with a TraceGold TG-5SilMS column (Thermo) operating under the following conditions: split ratio = 20-1, split flow = 24 μl/minute, purge flow = 5 ml/minute, carrier mode = Constant Flow, and carrier flow rate = 1.2 ml/minute. The GC oven temperature gradient was as follows: 80°C for 3 minutes, increasing at a rate of 20°C/minute to 280°C, and holding at a temperature at 280°C for 8 minutes.
Methods Filename:GC_Method_Tissue.pdf
Instrument Name:Thermo Trace 1310
Column Name:Thermo TraceGold TG-5SilMS
Chromatography Type:GC


MS ID:MS003361
Analysis ID:AN003607
Instrument Name:Thermo ISQ
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:The MS was operated from 3.90 to 21.00 minutes in EI mode (-70eV) using select ion monitoring (SIM). Data were QC normalized using NOREVA (PMID: 28525573).