Journal
CELL REPORTS
Volume 18, Issue 9, Pages 2269-2279Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.02.019
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Funding
- Innovative Medicines Initiative Joint Undertaking [155005]
- European Union's Seventh Framework Programme (FP7)
- EFPIA
- GlaxoSmithKline
- Faculty of Biology and Medicine of Lausanne
- Swiss National Science Foundation [33CSCO-122661, 33CS30-139468, 33CS30-148401, 3100A0B-128657]
- Swiss National Science Foundation (SNF) [3100A0B-128657] Funding Source: Swiss National Science Foundation (SNF)
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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.
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