Summary of Study ST002729

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 PR001693. The data can be accessed directly via it's Project DOI: 10.21228/M8VT66 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002729
Study TitleImproved Endurance Capacity of Diabetic Mice during SGLT2 Inhibition: Potential Role of AICARP, an Endogenous AMPK Activator.
Study SummaryDiabetes is associated with an increased risk of deleterious changes in muscle mass and function or sarcopenia, leading to physical inactivity and worsening glycemic control. Given the negative energy balance during sodium-glucose cotransporter 2 (SGLT2) inhibition, whether SGLT2 inhibitors affect skeletal muscle mass and function is a matter of concern. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains insufficiently explored. We aimed to explore the effects of canagliflozin (CANA), an SGLT2 inhibitor, on skeletal muscles in genetically diabetic db/db mice.
Institute
Medical Institute of Bioregulation, Kyushu University
Last NameTakahashi
First NameMasatomo
AddressMaidashi 3-1-1, Higashi-ku, Fukuoka, Fukuoka, 8128582, Japan
Emailm-takahashi@bioreg.kyushu-u.ac.jp
Phone0926426171
Submit Date2023-05-25
Raw Data AvailableYes
Raw Data File Type(s)mzML, mzXML, lcd
Analysis Type DetailLC-MS
Release Date2023-11-09
Release Version1
Masatomo Takahashi Masatomo Takahashi
https://dx.doi.org/10.21228/M8VT66
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001693
Project DOI:doi: 10.21228/M8VT66
Project Title:Role of AICARP, an endogenous AMPK activator, in improved endurance capacity in diabetic mice during SGLT2 inhibition.
Project Type:Wide targeted metabolomics & lipidomics
Project Summary:Diabetes is often associated with increased risk of deleterious muscle mass and function or sarcopenia, thus leading to physical inactivity and metabolic disorders. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an oral antidiabetic drug that promotes urinary excretion of glucose in the renal proximal tubules. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains elusive. Here, we examined the differential effect of CANA on the oxidative soleus and glycolytic EDL muscles from genetically obese diabetic db/db mice.
Institute:Medical Institute of Bioregulation, Kyushu University
Department:Metabolomics
Laboratory:Bamba lab.
Last Name:Takahashi
First Name:Masatomo
Address:Maidashi 3-1-1, Higashi-ku, Fukuoka, Fukuoka, 8128582, Japan
Email:m-takahashi@bioreg.kyushu-u.ac.jp
Phone:0926426171
Publications:https://onlinelibrary.wiley.com/doi/full/10.1002/jcsm.13350

Subject:

Subject ID:SU002835
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Animal Treatment
SA27474015db/db Cana
SA27474113db/db Cana
SA27474261db/db Cana
SA27474314db/db Cana
SA27474462db/db Cana
SA27474516db/db Cana
SA27474664db/db Cana
SA27474763db/db Cana
SA27474860db/db vehicle
SA27474957db/db vehicle
SA27475011db/db vehicle
SA27475112db/db vehicle
SA27475210db/db vehicle
SA2747539db/db vehicle
SA27475458db/db vehicle
SA27475559db/db vehicle
SA27472024db/+ Cana
SA27472123db/+ Cana
SA27472221db/+ Cana
SA2747237db/+ Cana
SA27472422db/+ Cana
SA2747258db/+ Cana
SA2747266db/+ Cana
SA2747275db/+ Cana
SA27472820db/+ vehicle
SA2747291db/+ vehicle
SA27473052db/+ vehicle
SA27473151db/+ vehicle
SA27473250db/+ vehicle
SA27473318db/+ vehicle
SA27473449db/+ vehicle
SA27473519db/+ vehicle
SA2747363db/+ vehicle
SA2747372db/+ vehicle
SA27473817db/+ vehicle
SA2747394db/+ vehicle
Showing results 1 to 36 of 36

Collection:

Collection ID:CO002828
Collection Summary:All mice were housed in a pathogen-free facility and maintained on a 12-h light and 12-h dark cycle with free access to normal chow diet and water. CANA was mixed at 0.03% (w/w) with CRF-1 and administered to 8-week-old db/+ and db/db mice for 4 weeks. Food intake was calculated for 3 consecutive days each week using the mouse feeder MF-4S. At the end of the experiments, 6 h-fasted mice were anesthetized with isoflurane and blood samples were obtained from the inferior vena cava. Skeletal muscles including soleus and extensor digitorum longus were immediately frozen and stored at -80°C for metabolome and lipidome analysis.
Sample Type:Skeletal muscles

Treatment:

Treatment ID:TR002844
Treatment Summary:All mice were free access to normal chow diet and water. CANA was mixed at 0.03% (w/w) with CRF-1 and administered to 8-week-old db/+ and db/db mice for 4 weeks.

Sample Preparation:

Sampleprep ID:SP002841
Sampleprep Summary:Metabolites were extracted from frozen and crushed skeletal muscle (~10 mg) or serum (20 uL) with 1 mL of solvent mixture (methanol:chloroform:water = 10:4:4, v/v/v) containing piperazine-1,4-bis (2-ethanesulfonic acid) (PIPES) (0.63 umol/L), 2-bromohypoxanthine (0.13 umol/L), free fatty acid (FA) 16:0 (13C16) (0.13 umol/L), diacylglycerol (DG) 15:0-18:1 (d7) (0.15 umol/L), and triacylglycerol (TG) 15:0-18:1 (d7) -15:0 (0.35 umol/L) as internal standards. The samples were vigorously mixed for 1 min and sonicated for 5 min. The extracts were then centrifuged at 16,000 × g for 5 min at 4°C, and the resultant supernatant was collected. Protein concentrations in the pellets were determined using a Pierce BCA Protein Assay Kit (Thermo Fisher Scientific, Massachusetts, USA). The collected supernatant (700 uL) was mixed with 235 uL of chloroform, and 155 uL of water, and then centrifuged at 16,000 × g for 5 min at 4°C. The aqueous (upper) layer (400 µL) was evaporated under vacuum, dried extracts were stored at −80°C until targeted polar metablome analysis. Prior to analysis, the dried aqueous layer was reconstituted in 50 uL of water. The organic (lower) layer (200 µL) was dried under a nitrogen stream, dried extracts were stored at −80°C until targeted lipidome analysis. Prior to analysis, the organic aqueous layer was reconstituted in 80 µL of methanol/chloroform (1/1, v/v)

Combined analysis:

Analysis ID AN004423 AN004424 AN004425 AN004426
Analysis type MS MS MS MS
Chromatography type Ion exchange Reversed phase Reversed phase Normal phase
Chromatography system Thermo Dionex ICS-5000+ Shimadzu Nexera X2 Shimadzu Nexera X2 Shimadzu Nexera UC
Column Dionex IonPac AS11-HC (250 x 2mm,4um) Merck Discovery HS F5 (PFP) (150 x 2.1mm,3um) GL Sciences Inert Sustain C18 (150 × 2.1mm, 3um) Waters ACQUITY UPC2 Torus DEA (100 x 3.0mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Triple quadrupole
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Shimadzu LCMS-8060
Ion Mode UNSPECIFIED UNSPECIFIED POSITIVE UNSPECIFIED
Units relative peak area relative peak area concentration (pmol/mg-protein) relative peak area

Chromatography:

Chromatography ID:CH003322
Chromatography Summary:Anionic polar metabolites (i.e., organic acids, sugar phosphates, nucleotides, etc.) were analyzed via IC/HRMS/MS.
Instrument Name:Thermo Dionex ICS-5000+
Column Name:Dionex IonPac AS11-HC (250 x 2mm,4um)
Column Temperature:30℃
Flow Gradient:10-100%A, 0-24.0 min, 100%A, 24.0-27.0 min, 100-10%A, 27.0-27.1 min, 10%A, 27.1-35.0 min
Flow Rate:0.3 mL/min
Solvent A:100 mM KOH in H2O
Solvent B:1 mM ammonium acetate in MeOH
Chromatography Type:Ion exchange
  
Chromatography ID:CH003323
Chromatography Summary:Cationic polar metabolites (i.e., amino acids, bases, nucleosides, etc) were analyzed via PFPP-LC/HRMS/MS.
Instrument Name:Shimadzu Nexera X2
Column Name:Merck Discovery HS F5 (PFP) (150 x 2.1mm,3um)
Column Temperature:40℃
Flow Gradient:0%B, 0-5.0 min, 0-40%B, 5.0-15.0 min, 40-100%B, 15.0-15.1 min, 100%B, 15.1-18.0 min, 100-0%B, 18.0-18.1 min, 0%B, 18.1-25.0 min
Flow Rate:0.25 mL/min
Solvent A:0.1% formic acid in H2O
Solvent B:ACN
Chromatography Type:Reversed phase
  
Chromatography ID:CH003324
Chromatography Summary:Acyl-CoA and acyl-carnitine were analyzed via C18-LC/HRMS/MS.
Instrument Name:Shimadzu Nexera X2
Column Name:GL Sciences Inert Sustain C18 (150 × 2.1mm, 3um)
Column Temperature:40℃
Flow Gradient:0-13.0 min, 2-95%B, 13.0-20.0 min, 95%B, 20.0-20.1 min, 95-2%B, 20.1-25.0 min, 2%B
Flow Rate:0.3 mL/min
Solvent A:5 mM ammonium acetate in H2O
Solvent B:ACN
Chromatography Type:Reversed phase
  
Chromatography ID:CH003325
Chromatography Summary:Fatty acids (FA), diacylglycerols (DG), and triacylglycerols (TG) were analyzed via Normal phase SFC/MS/MS.
Instrument Name:Shimadzu Nexera UC
Column Name:Waters ACQUITY UPC2 Torus DEA (100 x 3.0mm, 1.7um)
Column Temperature:50℃
Flow Gradient:0-1.0 min, 1%B, 1.0-24.0 min, 1-75%B, 24.0-26.0 min, 75%B, 26.0-26.1 min, 75-1%B, 26.1-30.0 min, 1%B
Flow Rate:1.0 mL/min
Solvent A:CO2
Solvent B:0.1% (w/v) ammonium acetate in MeOH/H2O (95/5)
Chromatography Type:Normal phase
Solvent C:0.1% (w/v) ammonium acetate in MeOH/H2O (95/5)

MS:

MS ID:MS004170
Analysis ID:AN004423
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: FullMS (posi/nega) Data processing/software: Reifycs Cascade ver. 1.0
Ion Mode:UNSPECIFIED
  
MS ID:MS004171
Analysis ID:AN004424
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: FullMS (posi/nega) Data processing/software: Reifycs Cascade ver. 1.0
Ion Mode:UNSPECIFIED
  
MS ID:MS004172
Analysis ID:AN004425
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS acquisition: FullMS (posi) Data processing/software: Reifycs Cascade ver. 1.0
Ion Mode:POSITIVE
  
MS ID:MS004173
Analysis ID:AN004426
Instrument Name:Shimadzu LCMS-8060
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:MS acquisition: MRM mode (posi/nega) Data processing/software: Multi-ChromatoAnalyst (mCAT) ver.23
Ion Mode:UNSPECIFIED
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