Summary of Study ST000198

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 PR000169. The data can be accessed directly via it's Project DOI: 10.21228/M8N88K This work is supported by NIH grant, U2C- DK119886.

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Study IDST000198
Study TitleLiver and Plasma metaboites for 13C-glucose load in wild type, LIRKO and LIRFKO mice
Study TypeAcyl-carnitine analysis (plasma)
Study SummaryFoxO proteins are major targets of insulin action. To better define the role of FoxO1 in mediating insulin effects in the liver, we generated liver-specific insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice. Here we show that LIRKO mice are severely insulin resistant based on glucose, insulin and C-peptide levels, and glucose and insulin tolerance tests, and genetic deletion of hepatic FoxO1 reverses these effects. 13C-glucose and insulin clamp studies indicate that regulation of both hepatic glucose production (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are also restored in LIRFKO mice corresponding to changes in gene expression. We conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects of insulin are sufficient to maintain normal whole-body and hepatic glucose metabolism when liver FoxO1 activity is disrupted. Research is published: http://www.nature.com/ncomms/2015/150512/ncomms8079/full/ncomms8079.html
Institute
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
Submit Date2015-06-10
Num Groups5
Total Subjects40
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size32 M
Analysis Type DetailLC-MS
Release Date2015-12-28
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8N88K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN000300
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1200
Column Waters Acquity HSS T3 (50 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Agilent 6490 QQQ
Ion Mode POSITIVE
Units pmol/mg sample

Chromatography:

Chromatography ID:CH000221
Methods ID:AQM050
Methods Filename:QM-004-Xbridg2mm_ACar+_MRM-Insert.m.zip
Instrument Name:Agilent 1200
Column Name:Waters Acquity HSS T3 (50 x 2.1mm,1.8um)
Chromatography Type:Reversed phase
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