| Circulating sphingolipid biomarkers in models of type 1 diabetes. | |
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MedLine Citation:
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PMID: 21068007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alterations in lipid metabolism may contribute to diabetic complications. Sphingolipids are essential components of cell membranes and have essential roles in homeostasis and in the initiation and progression of disease. However, the role of sphingolipids in type 1 diabetes remains largely unexplored. Therefore, we sought to quantify sphingolipid metabolites by LC-MS/MS from two animal models of type 1 diabetes (streptozotocin-induced diabetic rats and Ins2(Akita) diabetic mice) to identify putative therapeutic targets and biomarkers. The results reveal that sphingosine-1-phosphate (So1P) is elevated in both diabetic models in comparison to respective control animals. In addition, diabetic animals demonstrated reductions in plasma levels of omega-9 24:1 (nervonic acid)-containing ceramide, sphingomyelin, and cerebrosides. Reduction of 24:1-esterfied sphingolipids was also observed in liver and heart. Nutritional stress via a high-fat diet also reduced 24:1 content in the plasma and liver of mice, exacerbating the decrease in some cases where diabetes was also present. Subcutaneous insulin corrected both circulating So1P and 24:1 levels in the murine diabetic model. Thus, changes in circulating sphingolipids, as evidenced by an increase in bioactive So1P and a reduction in cardio- and neuro-protective omega-9 esterified sphingolipids, may serve as biomarkers for type 1 diabetes and represent novel therapeutic targets. |
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Authors:
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Todd E Fox; Maria C Bewley; Kellee A Unrath; Michelle M Pedersen; Robert E Anderson; Dae Young Jung; Leonard S Jefferson; Jason K Kim; Sarah K Bronson; John M Flanagan; Mark Kester |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-10 |
Journal Detail:
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Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-14 Completed Date: 2011-05-27 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 509-17 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Animals Biological Markers / blood, chemistry, metabolism Diabetes Mellitus, Experimental / blood, metabolism Diabetes Mellitus, Type 1 / blood*, genetics, metabolism Disease Models, Animal Fatty Acids / blood Female Insulin / genetics, pharmacology Liver / drug effects, metabolism Lysophospholipids / metabolism Male Mice Mutation Myocardium / metabolism Rats Sphingolipids / blood*, chemistry, metabolism Sphingosine / analogs & derivatives, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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EY018336/EY/NEI NIH HHS; R01 EY018336-03/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Fatty Acids; 0/Insulin; 0/Lysophospholipids; 0/Sphingolipids; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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