Summary of study ST000516

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 PR000383. The data can be accessed directly via it's Project DOI: 10.21228/M8JG7B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  |  Download all metabolite data  |  Download mwTab file (text)   |  Download mwTab file(JSON)
Study IDST000516
Study TitleMeasuring amino acid metabolites in insulin resistant and insulin deficient mouse tissue models
Study SummaryTo compare models of insulin resistance to a model of loss of insulin signaling, we will also determine amino acid metabolites from muscle, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.
Institute
Mayo Clinic
Last NameO'Neill
First NameBrian
AddressOne Joslin Place, Boston, MA 02215
Emailbrian.o'neill@joslin.harvard.edu
Phone617-309-2400
Submit Date2016-12-07
Analysis Type DetailLC-MS
Release Date2018-12-11
Release Version1
Brian O'Neill Brian O'Neill
https://dx.doi.org/10.21228/M8JG7B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000383
Project DOI:doi: 10.21228/M8JG7B
Project Title:Mayo Metabolomics Pilot and Feasibility Award: Role of muscle insulin and IGF-1 signaling on serum and muscle metabolite profiles
Project Summary:Skeletal muscle insulin resistance is a cardinal feature of the pathogenesis of type 2 diabetes. Insulin and IGF-1 signal through their highly related receptors to impact on many aspects of muscle physiology including glucose homeostasis, protein metabolism, and mitochondrial function. Early physiological studies, as well as recent large scale metabolomic studies, have shown that changes in specific pools of circulating amino acid metabolites, such as branched chain amino acids (BCAAs), are associated with insulin resistance and can predict future diabetes, but the source and impact of these changes in amino acids are not fully understood. We have recently generated mice which lack insulin receptors (IR) or IGF-1 receptors (IGF1R) or both in muscle using Cre lox recombination. We find that mice which lack only IR or only IGF1R in muscle show minimal changes in muscle mass, but do display increases in proteasomal activity and autophagy in muscle. On the other hand, mice with combined loss of both IR and IGF1R display markedly decreased muscle mass and enhanced degradation pathways, associated with increased protein synthesis, and display changes in mitochondrial gene regulation, indicating that both receptors can compensate to some extent for loss of the other. We hypothesize that IR and IGF1R signaling in muscle coordinate amino acid metabolite turnover and fuel substrate/mitochondrial metabolism, and that in insulin resistant states, changes in protein metabolism and mitochondrial function disrupt relative proportions of amino acid metabolites, which in turn contribute to diabetes risk and/or muscle pathology. We propose to test this hypothesis by performing large scale metabolomics on serum and muscle from mice lacking IR, IGF1R or both in muscle, and we will compare these changes to both insulin deficient streptozotocin-treated and insulin resistant diet-induced obese mouse models. To gain insight into which pathways are critical for metabolite changes, we will also treat mice with specific inhibitors of mTOR, a common protein synthesis pathway, as well as inhibitors of autophagy or proteasomal degradation and determine metabolite concentrations in muscle and serum. These studies will identify specific pathways that impact amino acid and mitochondrial metabolite flux which are perturbed in insulin resistant states, and potentially provide insights into how changes in amino acid metabolites contribute to diabetes risk.
Institute:Mayo Clinic
Last Name:O'Neill
First Name:Brian
Address:One Joslin Place, Boston, MA 02215
Email:brian.o'neill@joslin.harvard.edu
Phone:617-309-2400

Subject:

Subject ID:SU000538
Subject Type:Mouse
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammal

Factors:

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

mb_sample_id local_sample_id group
SA027076ms5630-4control
SA027077ms5630-2control
SA027078ms5630-1control
SA027079ms5630-5control
SA027080ms5630-6control
SA027081ms5630-3control
SA027046ms5630-14Fox0 TKO
SA027047ms5630-13Fox0 TKO
SA027048ms5630-15Fox0 TKO
SA027049ms5630-16Fox0 TKO
SA027050ms5630-18Fox0 TKO
SA027051ms5630-17Fox0 TKO
SA027052ms5630-12MIGIRKO
SA027053ms5630-11MIGIRKO
SA027054ms5630-9MIGIRKO
SA027055ms5630-10MIGIRKO
SA027056ms5630-8MIGIRKO
SA027057ms5630-7MIGIRKO
SA027058ms5630-24QKO
SA027059ms5630-23QKO
SA027060ms5630-22QKO
SA027061ms5630-21QKO
SA027062ms5630-20QKO
SA027063ms5630-19QKO
SA027064ms5630-26STZ
SA027065ms5630-27STZ
SA027066ms5630-29STZ
SA027067ms5630-30STZ
SA027068ms5630-25STZ
SA027069ms5630-28STZ
SA027070ms5630-33STZ FoxO TKO
SA027071ms5630-34STZ FoxO TKO
SA027072ms5630-35STZ FoxO TKO
SA027073ms5630-36STZ FoxO TKO
SA027074ms5630-32STZ FoxO TKO
SA027075ms5630-31STZ FoxO TKO
Showing results 1 to 36 of 36

Collection:

Collection ID:CO000532
Collection Summary:To determine the role of FoxO transcription factors in muscle atrophy and increased autophagy in MIGIRKO mice, we crossed MIGIRKO (lacking IR and IGF1R) mice with mice in which FoxO1, FoxO3, and FoxO4 genes were floxed to delete all the major isoforms of FoxO expressed in muscle. Mice in which 5 separate genes — IR, Igf1r, FoxO1, FoxO3, and FoxO4 — were specifically deleted in muscle (muscle quintuple-knockout mice, hereafter referred to as QKO mice); were born in normal Mendelian ratios, and appeared normal both on external inspection and following dissection compared with littermate controls and with muscle FoxO1/3/4 triple-knockout mice (FoxO TKO). Streptozotocin (STZ) treated mice were used as a model of insulin deficient diabetes.
Sample Type:Muscle

Treatment:

Treatment ID:TR000552
Treatment Summary:To determine the relevance of the changes in M-IR-/-, M-IGF1R-/- , and MIGIRKO mice to insulin resistant states, we will perform large scale metabolomics and determine amino acid and TCA cycle metabolites in muscle and serum from 5 mice fed chow diet or 5 fed a high fat diet (HFD) for 8 weeks. Lastly, to compare models of insulin resistance to a model of loss of insulin signaling, we will also determine muscle and serum metabolites in 5 control and 5 streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.

Sample Preparation:

Sampleprep ID:SP000545
Sampleprep Summary:Concentration of amino acids in muscle tissue

Combined analysis:

Analysis ID AN000790
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity
Column Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Quantum Ultra
Ion Mode POSITIVE
Units picomoles/mg

Chromatography:

Chromatography ID:CH000566
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS000697
Analysis ID:AN000790
Instrument Name:Thermo Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
  logo