Summary of Study ST000551

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.

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Study IDST000551
Study TitleInvestigating large scale metabolomics in mice tissue lacking insulin receptors and IGF-1 receptors
Study SummaryLarge scale metabolomics from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice tissue. Also compare mice on a chow diet to mice on a high fat diet (HFD).
Institute
Mayo Clinic
Last NameO'Neill
First NameBrian
AddressOne Joslin Place, Boston, MA 02215
Emailbrian.o'neill@joslin.harvard.edu
Phone617-309-2400
Submit Date2017-02-03
Analysis Type DetailLC-MS
Release Date2019-03-06
Release Version1
Brian O'Neill Brian O'Neill
https://dx.doi.org/10.21228/M8JG7B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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:SU000573
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 Genotype Diet
SA02853313jan15_35-r001_1CD Irlox Chow
SA02853413jan15_35-r002_1CD Irlox Chow
SA02853513jan15_25-r001_1CD Irlox Chow
SA02853613jan15_25-r002_1CD Irlox Chow
SA02853703mar15_35-r003_2CD Irlox Chow
SA02853803mar15_25-r001_2CD Irlox Chow
SA02853903mar15_35-r004_2CD Irlox Chow
SA02854003mar15_25-r002_2CD Irlox Chow
SA02854103mar15_08-r002_2CD Irlox Chow
SA02854213jan15_06-r002_1CD Irlox Chow
SA02854313jan15_06-r001_1CD Irlox Chow
SA02854403mar15_06-r001_2CD Irlox Chow
SA02854503mar15_06-r002_2CD Irlox Chow
SA02854603mar15_08-r001_2CD Irlox Chow
SA02854713jan15_08-r002_1CD Irlox Chow
SA02854813jan15_08-r001_1CD Irlox Chow
SA02854913jan15_09-r001_1Control IGFR lox Chow
SA02855013jan15_09-r002_1Control IGFR lox Chow
SA02855103mar15_31-r001_2Control IGFR lox Chow
SA02855213jan15_31-r002_1Control IGFR lox Chow
SA02855313jan15_13-r002_1Control IGFR lox Chow
SA02855403mar15_31-r002_2Control IGFR lox Chow
SA02855513jan15_13-r001_1Control IGFR lox Chow
SA02855603mar15_09-r002_2Control IGFR lox Chow
SA02855713jan15_31-r001_1Control IGFR lox Chow
SA02855803mar15_13-r002_2Control IGFR lox Chow
SA02855903mar15_09-r001_2Control IGFR lox Chow
SA02856003mar15_13-r001_2Control IGFR lox Chow
SA02857703mar15_28-r002_2Control Irlox Chow
SA02857803mar15_28-r001_2Control Irlox Chow
SA02857903mar15_21-r003_2Control Irlox Chow
SA02858013jan15_18-r001_1Control Irlox Chow
SA02858103mar15_20-r001_2Control Irlox Chow
SA02858203mar15_18-r002_2Control Irlox Chow
SA02858303mar15_18-r001_2Control Irlox Chow
SA02858413jan15_28-r002_1Control Irlox Chow
SA02858513jan15_28-r001_1Control Irlox Chow
SA02858603mar15_21-r002_2Control Irlox Chow
SA02858703mar15_20-r002_2Control Irlox Chow
SA02858813jan15_20-r002_1Control Irlox Chow
SA02858913jan15_21-r002_1Control Irlox Chow
SA02859013jan15_20-r001_1Control Irlox Chow
SA02859113jan15_18-r002_1Control Irlox Chow
SA02859213jan15_21-r001_1Control Irlox Chow
SA02856103mar15_30-r002_2Control IRlox IGFR lox Chow
SA02856203mar15_30-r001_2Control IRlox IGFR lox Chow
SA02856303mar15_29-r001_2Control IRlox IGFR lox Chow
SA02856403mar15_29-r002_2Control IRlox IGFR lox Chow
SA02856503mar15_27-r001_2Control IRlox IGFR lox Chow
SA02856613jan15_29-r001_1Control IRlox IGFR lox Chow
SA02856713jan15_32-r002_1Control IRlox IGFR lox Chow
SA02856813jan15_29-r002_1Control IRlox IGFR lox Chow
SA02856913jan15_30-r001_1Control IRlox IGFR lox Chow
SA02857013jan15_30-r002_1Control IRlox IGFR lox Chow
SA02857103mar15_32-r001_2Control IRlox IGFR lox Chow
SA02857203mar15_27-r002_2Control IRlox IGFR lox Chow
SA02857303mar15_32-r002_2Control IRlox IGFR lox Chow
SA02857413jan15_27-r001_1Control IRlox IGFR lox Chow
SA02857513jan15_27-r002_1Control IRlox IGFR lox Chow
SA02857613jan15_32-r001_1Control IRlox IGFR lox Chow
SA02859313jan15_39-r001_1HFD Irlox High Fat Diet
SA02859413jan15_04-r002_1HFD Irlox High Fat Diet
SA02859513jan15_39-r002_1HFD Irlox High Fat Diet
SA02859613jan15_38-r001_1HFD Irlox High Fat Diet
SA02859713jan15_38-r002_1HFD Irlox High Fat Diet
SA02859813jan15_11-r001_1HFD Irlox High Fat Diet
SA02859903mar15_04-r001_2HFD Irlox High Fat Diet
SA02860013jan15_11-r002_1HFD Irlox High Fat Diet
SA02860113jan15_10-r002_1HFD Irlox High Fat Diet
SA02860213jan15_10-r001_1HFD Irlox High Fat Diet
SA02860313jan15_04-r001_1HFD Irlox High Fat Diet
SA02860403mar15_38-r002_2HFD Irlox High Fat Diet
SA02860503mar15_38-r001_2HFD Irlox High Fat Diet
SA02860603mar15_10-r002_2HFD Irlox High Fat Diet
SA02860703mar15_10-r001_2HFD Irlox High Fat Diet
SA02860803mar15_11-r002_2HFD Irlox High Fat Diet
SA02860903mar15_11-r001_2HFD Irlox High Fat Diet
SA02861003mar15_04-r002_2HFD Irlox High Fat Diet
SA02861103mar15_39-r004_2HFD Irlox High Fat Diet
SA02861203mar15_39-r003_2HFD Irlox High Fat Diet
SA02861313jan15_14-r002_1IGFRKO IGFR -/- Chow
SA02861413jan15_14-r001_1IGFRKO IGFR -/- Chow
SA02861513jan15_34-r001_1IGFRKO IGFR -/- Chow
SA02861603mar15_14-r002_2IGFRKO IGFR -/- Chow
SA02861703mar15_23-r001_2IGFRKO IGFR -/- Chow
SA02861813jan15_23-r002_1IGFRKO IGFR -/- Chow
SA02861903mar15_23-r002_2IGFRKO IGFR -/- Chow
SA02862013jan15_34-r002_1IGFRKO IGFR -/- Chow
SA02862103mar15_12-r002_2IGFRKO IGFR -/- Chow
SA02862203mar15_14-r001_2IGFRKO IGFR -/- Chow
SA02862303mar15_12-r001_2IGFRKO IGFR -/- Chow
SA02862413jan15_12-r002_1IGFRKO IGFR -/- Chow
SA02862503mar15_05-r002_2IGFRKO IGFR -/- Chow
SA02862603mar15_05-r001_2IGFRKO IGFR -/- Chow
SA02862713jan15_23-r001_1IGFRKO IGFR -/- Chow
SA02862813jan15_05-r002_1IGFRKO IGFR -/- Chow
SA02862913jan15_05-r001_1IGFRKO IGFR -/- Chow
SA02863013jan15_12-r001_1IGFRKO IGFR -/- Chow
SA02863103mar15_34-r003_2IGFRKO IGFR -/- Chow
SA02863203mar15_34-r004_2IGFRKO IGFR -/- Chow
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Collection:

Collection ID:CO000567
Collection Summary:mouse gastrocnemius tissue
Sample Type:Muscle

Treatment:

Treatment ID:TR000587
Treatment Summary:Mice lacking insulin receptors (IR -/- genotype, IRKO group), or IGF-1 receptors (ICF-1 -/- genotype, IGFRKO group), or both (MIGIRKO group) were generated using Cre lox recombination. Controls (group control and CD) were IR lox/lox, IGF-1 lox/lox, or both genotypes. Additional, 10 mice were included that were fed different diets for 8 weeks, chow or high fat diet (group HFD).

Sample Preparation:

Sampleprep ID:SP000580
Sampleprep Summary:large scale metabolomics in mouse gastrocnemius tissue

Combined analysis:

Analysis ID AN000841 AN000842
Analysis type MS MS
Chromatography type HILIC Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters Acquity BEH Amide (150 x 2.1mm,1.7um) Waters Acquity HSS C18 (150 x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Agilent 6550 QTOF Agilent 6550 QTOF
Ion Mode POSITIVE POSITIVE
Units intensity intensity

Chromatography:

Chromatography ID:CH000601
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
Chromatography Type:HILIC
  
Chromatography ID:CH000602
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity HSS C18 (150 x 2.1mm,1.8um)
Chromatography Type:Reversed phase

MS:

MS ID:MS000742
Analysis ID:AN000841
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
  
MS ID:MS000743
Analysis ID:AN000842
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
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