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Int J Mol Sci. 2017 Jul 15;18(7). pii: E1532. doi: 10.3390/ijms18071532.

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

Author information

1
Department of General Pharmacology and Toxicology, Goethe University Hospital, 60590 Frankfurt am Main, Germany. koch@med.uni-frankfurt.de.
2
Department of General Pharmacology and Toxicology, Goethe University Hospital, 60590 Frankfurt am Main, Germany. georgios.grammatikos@kgu.de.
3
Department of Medicine I, Goethe University Hospital, 60590 Frankfurt am Main, Germany. georgios.grammatikos@kgu.de.
4
Department of Clinical Pharmacology, Goethe University Hospital, 60590 Frankfurt am Main, Germany. labocha@med.uni-frankfurt.de.
5
Fraunhofer Institute of Molecular Biology and Applied Ecology-Project Group Translational Medicine and Pharmacology (IME-TMP), 60590 Frankfurt am Main, Germany. schreiber@med.uni-frankfurt.de.
6
Department of Clinical Pharmacology, Goethe University Hospital, 60590 Frankfurt am Main, Germany. thomas@med.uni-frankfurt.de.
7
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, 60590 Frankfurt am Main, Germany. franziskabruns85@gmail.com.
8
Department of General Pharmacology and Toxicology, Goethe University Hospital, 60590 Frankfurt am Main, Germany. pfeilschifter@em.uni-frankfurt.de.
9
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, 60590 Frankfurt am Main, Germany. badenhoop@em.uni-frankfurt.de.
10
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, Goethe University Hospital, 60590 Frankfurt am Main, Germany. Marissa.Penna-Martinez@kgu.de.

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.

KEYWORDS:

Type 2 Diabetes mellitus; ceramide; dihydroceramide; sphingolipid metabolism; sphingosine 1-phosphate; vitamin D

PMID:
28714882
PMCID:
PMC5536020
DOI:
10.3390/ijms18071532
[Indexed for MEDLINE]
Free PMC Article

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