Summary of study ST000549

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

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Study IDST000549
Study TitleInvestigating large scale metabolomics in mice serum lacking insulin receptors and IGF-1 receptors
Study SummaryLarge scale metabolomics from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice serum. 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:SU000571
Subject Type:Mouse
Subject Species:Mus musculus
Taxonomy ID:10900
Species Group:Mammal

Factors:

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

mb_sample_id local_sample_id Group Genotype
SA02832619jan15_08CD Irlox
SA02832705jan15_35-r001CD Irlox
SA02832805jan15_35-r002CD Irlox
SA02832905jan15_25-r001CD Irlox
SA02833019jan15_06CD Irlox
SA02833119jan15_25CD Irlox
SA02833219jan15_65CD Irlox
SA02833305jan15_08-r002CD Irlox
SA02833419jan15_75CD Irlox
SA02833505jan15_25-r002CD Irlox
SA02833619jan15_48CD Irlox
SA02833705jan15_06-r001CD Irlox
SA02833819jan15_46CD Irlox
SA02833905jan15_06-r002CD Irlox
SA02834005jan15_08-r001CD Irlox
SA02834119jan15_35CD Irlox
SA02834219jan15_09Control IGFR lox
SA02834305jan15_13-r001Control IGFR lox
SA02834405jan15_13-r002Control IGFR lox
SA02834519jan15_71Control IGFR lox
SA02834619jan15_13Control IGFR lox
SA02834705jan15_31-r002Control IGFR lox
SA02834819jan15_31Control IGFR lox
SA02834919jan15_53Control IGFR lox
SA02835019jan15_49Control IGFR lox
SA02835105jan15_09-r001Control IGFR lox
SA02835205jan15_31-r001Control IGFR lox
SA02835305jan15_09-r002Control IGFR lox
SA02837019jan15_58Control Irlox
SA02837119jan15_21Control Irlox
SA02837219jan15_61Control Irlox
SA02837319jan15_28Control Irlox
SA02837405jan15_28-r001Control Irlox
SA02837519jan15_60Control Irlox
SA02837619jan15_20Control Irlox
SA02837705jan15_20-r001Control Irlox
SA02837805jan15_18-r002Control Irlox
SA02837905jan15_20-r002Control Irlox
SA02838005jan15_21-r002Control Irlox
SA02838105jan15_28-r002Control Irlox
SA02838205jan15_18-r001Control Irlox
SA02838305jan15_21-r001Control Irlox
SA02838419jan15_68Control Irlox
SA02838519jan15_18Control Irlox
SA02835419jan15_30Control IRlox IGFR lox
SA02835519jan15_32Control IRlox IGFR lox
SA02835605jan15_27-r002Control IRlox IGFR lox
SA02835719jan15_29Control IRlox IGFR lox
SA02835819jan15_27Control IRlox IGFR lox
SA02835905jan15_27-r001Control IRlox IGFR lox
SA02836019jan15_70Control IRlox IGFR lox
SA02836105jan15_32-r001Control IRlox IGFR lox
SA02836205jan15_30-r002Control IRlox IGFR lox
SA02836319jan15_67Control IRlox IGFR lox
SA02836419jan15_69Control IRlox IGFR lox
SA02836505jan15_30-r001Control IRlox IGFR lox
SA02836619jan15_72Control IRlox IGFR lox
SA02836705jan15_32-r002Control IRlox IGFR lox
SA02836805jan15_29-r001Control IRlox IGFR lox
SA02836905jan15_29-r002Control IRlox IGFR lox
SA02838605jan15_39-r001HFD Irlox
SA02838705jan15_39-r002HFD Irlox
SA02838805jan15_40-r001HFD Irlox
SA02838905jan15_04-r002HFD Irlox
SA02839005jan15_40-r002HFD Irlox
SA02839105jan15_38-r002HFD Irlox
SA02839219jan15_44HFD Irlox
SA02839305jan15_10-r002HFD Irlox
SA02839405jan15_11-r001HFD Irlox
SA02839505jan15_11-r002HFD Irlox
SA02839605jan15_10-r001HFD Irlox
SA02839705jan15_38-r001HFD Irlox
SA02839805jan15_04-r001HFD Irlox
SA02839919jan15_51HFD Irlox
SA02840019jan15_11HFD Irlox
SA02840119jan15_10HFD Irlox
SA02840219jan15_04-r001HFD Irlox
SA02840319jan15_50HFD Irlox
SA02840419jan15_78HFD Irlox
SA02840519jan15_79HFD Irlox
SA02840619jan15_38HFD Irlox
SA02840719jan15_39HFD Irlox
SA02840805jan15_23-r002IGFRKO IGFR -/-
SA02840905jan15_14-r002IGFRKO IGFR -/-
SA02841005jan15_14-r001IGFRKO IGFR -/-
SA02841119jan15_12IGFRKO IGFR -/-
SA02841205jan15_34-r001IGFRKO IGFR -/-
SA02841319jan15_14IGFRKO IGFR -/-
SA02841419jan15_74IGFRKO IGFR -/-
SA02841519jan15_63IGFRKO IGFR -/-
SA02841605jan15_34-r002IGFRKO IGFR -/-
SA02841719jan15_52IGFRKO IGFR -/-
SA02841819jan15_34IGFRKO IGFR -/-
SA02841919jan15_45IGFRKO IGFR -/-
SA02842005jan15_05-r002IGFRKO IGFR -/-
SA02842105jan15_05-r001IGFRKO IGFR -/-
SA02842219jan15_54IGFRKO IGFR -/-
SA02842305jan15_23-r001IGFRKO IGFR -/-
SA02842419jan15_23IGFRKO IGFR -/-
SA02842505jan15_12-r002IGFRKO IGFR -/-
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Collection:

Collection ID:CO000565
Collection Summary:mouse serum
Sample Type:Blood

Treatment:

Treatment ID:TR000585
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:SP000578
Sampleprep Summary:large scale metabolomics in mouse serum

Combined analysis:

Analysis ID AN000837 AN000838 AN000839
Analysis type MS MS MS
Chromatography type HILIC HILIC Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) Waters Acquity HSS C18 (150 x 2.1mm, 1.8um)
MS Type ESI ESI ESI
MS instrument type QTOF QTOF QTOF
MS instrument name Agilent 6550 QTOF Agilent 6550 QTOF Agilent 6550 QTOF
Ion Mode POSITIVE NEGATIVE POSITIVE
Units intensity intensity intensity

Chromatography:

Chromatography ID:CH000598
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
Chromatography Type:HILIC
  
Chromatography ID:CH000599
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity HSS C18 (150 x 2.1mm, 1.8um)
Chromatography Type:Reversed phase

MS:

MS ID:MS000738
Analysis ID:AN000837
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
  
MS ID:MS000739
Analysis ID:AN000838
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
  
MS ID:MS000740
Analysis ID:AN000839
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
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