Circulating sphingolipid biomarkers in models of type 1 diabetes
| Autor: | John M. Flanagan, Michelle M. Pedersen, Sarah K. Bronson, Robert E. Anderson, Dae Young Jung, Kellee A. Unrath, Todd E. Fox, Mark Kester, Leonard S. Jefferson, Maria C. Bewley, Jason K. Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Ceramide medicine.medical_treatment cerebrosides QD415-436 Biology Biochemistry Diabetes Mellitus Experimental nervonic acid sphingomyelin chemistry.chemical_compound Mice Endocrinology Sphingosine Internal medicine Diabetes mellitus medicine Animals Insulin Sphingosine-1-phosphate ceramide Alleles Research Articles Type 1 diabetes Sphingolipids Myocardium Fatty Acids Cell Biology medicine.disease Sphingolipid Rats Disease Models Animal Diabetes Mellitus Type 1 chemistry Liver Mutation sphingosine-1-phosphate lipidomics Female Lysophospholipids Sphingomyelin Biomarkers |
| Zdroj: | Journal of Lipid Research, Vol 52, Iss 3, Pp 509-517 (2011) |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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