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Vitamin D Supplementation Enhances C18(dihydro)ceramide Levels in Type 2 Diabetes Patients

 
: Koch, A.; Grammatikos, G.; Trautmann, S.; Schreiber, Y.; Thomas, D.; Bruns, F.; Pfeilschifter, J.; Badenhoop, K.; Penna-Martinez, M.

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International journal of molecular sciences 18 (2017), No.7, Art. 1532, 10 pp.
ISSN: 1422-0067
ISSN: 1661-6596
Deutsche Forschungsgemeinschaft DFG
SFB1039 "Lipid Signalling"
English
Journal Article, Electronic Publication
Fraunhofer IME ()

Abstract
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D froma placebo-controlled, randomized, and double-blind study were retrospectively analyzed. Once per week, patients received either 20 drops of Vigantol oil, corresponding to a daily dose of 1904 IU/d vitamin D (verum: n = 31), or a placebo oil consisting of medium chain triglycerides (placebo: n = 28). Blood samples were taken from all of the participants at three different time points: 1) at the beginning of the study (baseline), 2) after 6 months supplementation, and 3) after an additional 6 months of follow-up. Plasma sphingolipids were measured by high-performance liquid chromatography tandem mass spectrometry. At baseline and 6 months follow-up, no significant differences in plasma sphingolipid species were detected between the placebo and verum groups. After 6 months, vitamin D supplementation significantly enhanced plasma C18dihydroceramide (dhCer; N-stearoyl-sphinganine (d18:0/ 18: 0)) and C18ceramide (Cer; N-stearoyl-sphingosine (d18: 1/ 18: 0)) levels were observed in the verum group compared to the placebo group. This was accompanied by significantly higher 25-hydroxyvitamin D-3 (25(OH) D3) blood levels in patients receiving vitamin D compared to the placebo group. Taken together, vitamin D supplementation induced changes of the C18 chain-length-specific dhCer and Cer plasma levels in patients with T2D. The regulation of sphingolipid signaling by vitamin D may thus unravel a novel mechanism by which vitamin D can influence glucose utilization and insulin action. Whether this acts favorably or unfavorably for the progression of T2D needs to be clarified.

: http://publica.fraunhofer.de/documents/N-480594.html