Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator
AMP-activated protein kinase (AMPK) is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to localize renal nucleotides we f...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-05-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416301207 |
| _version_ | 1818261441943175168 |
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| author | Satoshi Miyamoto Cheng-Chih Hsu Gregory Hamm Manjula Darshi Maggie Diamond-Stanic Anne-Emilie Declèves Larkin Slater Subramaniam Pennathur Jonathan Stauber Pieter C. Dorrestein Kumar Sharma |
| author_facet | Satoshi Miyamoto Cheng-Chih Hsu Gregory Hamm Manjula Darshi Maggie Diamond-Stanic Anne-Emilie Declèves Larkin Slater Subramaniam Pennathur Jonathan Stauber Pieter C. Dorrestein Kumar Sharma |
| author_sort | Satoshi Miyamoto |
| collection | DOAJ |
| description | AMP-activated protein kinase (AMPK) is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to localize renal nucleotides we found that the diabetic kidney had a significant increase in glomerular ATP/AMP ratio. Untargeted MALDI-MSI analysis revealed that a specific sphingomyelin species (SM(d18:1/16:0)) accumulated in the glomeruli of diabetic and high-fat diet-fed mice compared with wild-type controls. In vitro studies in mesangial cells revealed that exogenous addition of SM(d18:1/16:0) significantly elevated ATP via increased glucose consumption and lactate production with a consequent reduction of AMPK and PGC1α. Furthermore, inhibition of sphingomyelin synthases reversed these effects. Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0) could be responsible for the enhanced ATP production via activation of the glycolytic pathway. |
| first_indexed | 2024-12-12T18:47:17Z |
| format | Article |
| id | doaj.art-6c9be6c85ddf4b35a4f0c92fffa17296 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T18:47:17Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-6c9be6c85ddf4b35a4f0c92fffa172962022-12-22T00:15:28ZengElsevierEBioMedicine2352-39642016-05-017C12113410.1016/j.ebiom.2016.03.033Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible MediatorSatoshi Miyamoto0Cheng-Chih Hsu1Gregory Hamm2Manjula Darshi3Maggie Diamond-Stanic4Anne-Emilie Declèves5Larkin Slater6Subramaniam Pennathur7Jonathan Stauber8Pieter C. Dorrestein9Kumar Sharma10Institute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USAImaBiotech, MS Imaging Department, Lille 59120, FranceInstitute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USAInstitute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USACenter for Renal Translational Medicine, Division of Nephrology-Hypertension, University of California San Diego, La Jolla, CA 92093, USAInstitute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAImaBiotech, MS Imaging Department, Lille 59120, FranceInstitute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USAInstitute of Metabolomic Medicine, University of California San Diego, La Jolla, CA 92093, USAAMP-activated protein kinase (AMPK) is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to localize renal nucleotides we found that the diabetic kidney had a significant increase in glomerular ATP/AMP ratio. Untargeted MALDI-MSI analysis revealed that a specific sphingomyelin species (SM(d18:1/16:0)) accumulated in the glomeruli of diabetic and high-fat diet-fed mice compared with wild-type controls. In vitro studies in mesangial cells revealed that exogenous addition of SM(d18:1/16:0) significantly elevated ATP via increased glucose consumption and lactate production with a consequent reduction of AMPK and PGC1α. Furthermore, inhibition of sphingomyelin synthases reversed these effects. Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0) could be responsible for the enhanced ATP production via activation of the glycolytic pathway.http://www.sciencedirect.com/science/article/pii/S2352396416301207Matrix-assisted laser desorption/ionization mass spectrometry imagingSphingomyelinChronic kidney diseaseATPAMPKGlycolysis |
| spellingShingle | Satoshi Miyamoto Cheng-Chih Hsu Gregory Hamm Manjula Darshi Maggie Diamond-Stanic Anne-Emilie Declèves Larkin Slater Subramaniam Pennathur Jonathan Stauber Pieter C. Dorrestein Kumar Sharma Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator EBioMedicine Matrix-assisted laser desorption/ionization mass spectrometry imaging Sphingomyelin Chronic kidney disease ATP AMPK Glycolysis |
| title | Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator |
| title_full | Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator |
| title_fullStr | Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator |
| title_full_unstemmed | Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator |
| title_short | Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator |
| title_sort | mass spectrometry imaging reveals elevated glomerular atp amp in diabetes obesity and identifies sphingomyelin as a possible mediator |
| topic | Matrix-assisted laser desorption/ionization mass spectrometry imaging Sphingomyelin Chronic kidney disease ATP AMPK Glycolysis |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416301207 |
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