Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans.

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State: Public
Version: Final published version
Serval ID
serval:BIB_78CB07C09AAA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans.
Journal
Cell reports
Author(s)
Wigger L., Cruciani-Guglielmacci C., Nicolas A., Denom J., Fernandez N., Fumeron F., Marques-Vidal P., Ktorza A., Kramer W., Schulte A., Le Stunff H., Liechti R., Xenarios I., Vollenweider P., Waeber G., Uphues I., Roussel R., Magnan C., Ibberson M., Thorens B.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
28/02/2017
Peer-reviewed
Oui
Volume
18
Number
9
Pages
2269-2279
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D). Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D.

Keywords
Adult, Aged, Animals, Biomarkers/blood, Blood Glucose/metabolism, Ceramides/blood, Diabetes Mellitus, Type 2/blood, Diabetes Mellitus, Type 2/metabolism, Disease Susceptibility/blood, Female, Glucose Intolerance/blood, Glucose Intolerance/metabolism, Glucose Tolerance Test/methods, Humans, Insulin/blood, Insulin Resistance/physiology, Lipids/blood, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Middle Aged, Prospective Studies, Sphingolipids/blood, T2D, biomarkers, ceramides, diabetes, dihydroceramides, glucose intolerance, high-fat diet, human, insulin sensitivity, lipidomics, metabolic challenge, mouse, prognostic, prospective cohort
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2017 18:28
Last modification date
20/08/2019 14:35
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