Endocrine Abstracts

Type 2 diabetes (T2D) patients have a high cardiovascular risk due to vascular inflammation and dyslipidaemia. Furthermore vitamin D (VD) deficiency is highly prevalent. Our aim was to elucidate the role of fatty acid receptors in inflammatory pathways and their regulation by VD. We therefore examined the VD effect on gene expression of Arachidonate 5-lipoxygenase (ALOX-5) and Sphingosine-1-phospate receptors (S1PR1 and S1PR2) in primary isolated monocytes of T2D patients and healthy controls (HC). CD14⁺ monocytes (Mo) were isolated from 20 healthy controls (HC) and 20 T2D patients and were treated for 24 h with / without 10⁻⁸ M calcitriol. Interleukin-1β as an inflammatory stimulant served as IL-1β_{control-cells}. CD14, ALOX-5, S1PR₁ and S1PR₂ mRNA expression levels were measured by TaqMan^™ analyses. 18s rRNA served as a house keeping gene. Gene expressions were defined as 2^{-[Ct (target)-Ct (18srRNA)]}. Calcitriol treatment significantly increased the CD14 gene expression in both HC (CD14 _calcitriol: 5059 vs. 2104; P=0.05) and T2D (CD14_calcitriol: 12176 vs. 6712; P=0.001) compared to the IL-1β_{control-cells}. The CD14 gene expression was noticeable increased in T2D patients compared to HC (P=0.002). Moreover ALOX-5 mRNA-levels were also increased by calcitriol compared to the IL-1β_{control-cells} in HC (ALOX-5_calcitriol: 1686 vs. 1004; P=0.02) and in T2D (ALOX-5_calcitriol: 2744 vs. 1372; P=9.1×10^-5). By comparing HC vs. T2D, it stands out that ALOX-5 mRNA-levels were higher in T2D patients compared to HC (P=0.01). Furthermore, the mRNA levels of S1PR₂ were significantly reduced in both HC (S1PR_2calcitriol: 5.75 vs. 25; P=10⁻⁶) and T2D (S1PR_2calcitriol: 5.96 vs. 36; P=0.001) compared to the IL-1β_{control-cells.} Interestingly, T2D patients mRNA levels of S1PR₂ of IL-1β_{control-cells} compared to HC were significantly higher (P=0.03). Calcitriol treatment did not change the mRNA levels of S1PR₂ by comparing HC vs. T2D. No significant changes of the S1PR₁ mRNA expression were observed in calcitriol treated Mo from HC and T2D patients. In vitro calcitriol increased the CD14 and ALOX-5 gene expression in HC and T2D-patients.However, the increase of CD14 and ALOX-5 gene expression in T2D appears to be disease specific. Further calcitriol had no impact on S1PR₁ -but on S1PR₂ mRNA expression. Although calcitriol reduced the gene expression of S1PR₂ both in T2D-patients and HC this was not discriminatory. These results provide novel insights into potential anti-inflammatory mechanisms of VD in type 2 diabetes.