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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Factors:

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

mb_sample_id local_sample_id treatment Strain
SA009991S00013165glucose IRF floxed
SA009992S00013145glucose IRF floxed
SA009985S00013144glucose IR floxed
SA009986S00013164glucose IR floxed
SA009987S00013163glucose IR floxed
SA009988S00013162glucose IR floxed
SA009989S00013142glucose IR floxed
SA009990S00013143glucose IR floxed
SA009993S00013154glucose LIRFKO
SA009994S00013153glucose LIRFKO
SA009995S00013175glucose LIRFKO
SA009996S00013173glucose LIRFKO
SA009997S00013152glucose LIRFKO
SA009998S00013172glucose LIRFKO
SA009999S00013174glucose LIRFKO
SA010000S00013155glucose LIRFKO
SA010001S00013166glucose LIRKO
SA010002S00013146glucose LIRKO
SA010003S00013151glucose LIRKO
SA010004S00013167glucose LIRKO
SA010005S00013168glucose LIRKO
SA010006S00013171glucose LIRKO
SA010007S00013170glucose LIRKO
SA010008S00013169glucose LIRKO
SA010009S00013148glucose LIRKO
SA010010S00013147glucose LIRKO
SA010011S00013150glucose LIRKO
SA010012S00013149glucose LIRKO
SA010013S00013140none IR floxed
SA010014S00013139none IR floxed
SA010015S00013137none IR floxed
SA010016S00013138none IR floxed
SA010017S00013136none IR floxed
SA010018S00013156none IR floxed
SA010019S00013159none IR floxed
SA010020S00013160none IR floxed
SA010021S00013141none IR floxed
SA010022S00013158none IR floxed
SA010023S00013157none IR floxed
SA010024S00013161none IR floxed
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