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Int. J. Mol. Sci. 2017, 18(7), 1532; doi:10.3390/ijms18071532

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

1
Department of General Pharmacology and Toxicology, Goethe University Hospital, 60590 Frankfurt am Main, Germany
2
Department of Medicine I, Goethe University Hospital, 60590 Frankfurt am Main, Germany
3
Department of Clinical Pharmacology, Goethe University Hospital, 60590 Frankfurt am Main, Germany
4
Fraunhofer Institute of Molecular Biology and Applied Ecology—Project Group Translational Medicine and Pharmacology (IME-TMP), 60590 Frankfurt am Main, Germany
5
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, 60590 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Received: 7 June 2017 / Revised: 7 July 2017 / Accepted: 11 July 2017 / Published: 15 July 2017
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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 from a 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 D3 (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. View Full-Text
Keywords: vitamin D; Type 2 Diabetes mellitus; sphingolipid metabolism; ceramide; dihydroceramide; sphingosine 1-phosphate vitamin D; Type 2 Diabetes mellitus; sphingolipid metabolism; ceramide; dihydroceramide; sphingosine 1-phosphate
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MDPI and ACS Style

Koch, A.; Grammatikos, G.; Trautmann, S.; Schreiber, Y.; Thomas, D.; Bruns, F.; Pfeilschifter, J.; Badenhoop, K.; Penna-Martinez, M. Vitamin D Supplementation Enhances C18(dihydro)ceramide Levels in Type 2 Diabetes Patients. Int. J. Mol. Sci. 2017, 18, 1532.

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