Correlation between Sirtuin 1 downregulation and reduced vitamin D receptor expression in patients with diabetic neuropathy.

IF 3.1 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Acta Diabetologica Pub Date : 2025-02-20 DOI:10.1007/s00592-025-02463-w

Andrea Latini, Giada De Benedittis, Chiara Morgante, Beatrice Gasperini, Ilenia D'Ippolito, Davide Lauro, Giuseppe Novelli, Cinzia Ciccacci, Vincenza Spallone, Paola Borgiani

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Abstract

Aims: We aimed to analyse Sirtuin 1 (SIRT1) and Vitamin D receptor (VDR) expression levels in the peripheral blood of patients with type 2 diabetes (T2D), characterized for the presence of diabetic neuropathy (DN), and to evaluate possible genetic factors that could influence the VDR expression levels.

Methods: Fifty-one participants with T2D, who underwent neurological assessment for DN were recruited. We quantified the mRNA levels of SIRT1 and VDR in peripheral blood mononuclear cells. Moreover, we analysed the methylation status and the rs2228570 genetic variant of VDR promoter.

Results: Patients with DN (n = 32) showed lower expression of SIRT1 (p_corr=0.018) and VDR (p_corr=0.009), compared to those without DN. Furthermore, we observed a positive correlation between the mRNA levels of SIRT1 and VDR (p = 0.01). The expression levels of these genes negatively correlated with the score based on cardiovascular reflex tests (CARTs score). Moreover, the variant allele of rs2228570 in the VDR gene was associated with higher expression of this gene compared to the wild-type allele (p = 0.003).

Conclusion: In patients with DN, both SIRT1 and VDR expression levels are reduced and interrelated. Low VDR expression levels could negatively affect SIRT1 transcription, thus influencing all the most pathogenetic pathways of DN regulated by this protein.

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糖尿病神经病变患者Sirtuin 1下调与维生素D受体表达降低的相关性

目的：分析以糖尿病性神经病变（DN）为特征的2型糖尿病（T2D）患者外周血中Sirtuin 1 （SIRT1）和维生素D受体（VDR）的表达水平，并评估可能影响VDR表达水平的遗传因素。方法：招募51例T2D患者，对DN进行神经学评估。我们量化外周血单个核细胞中SIRT1和VDR的mRNA水平。此外，我们还分析了VDR启动子的甲基化状态和rs2228570遗传变异。结果：与非DN患者相比，DN患者（n = 32） SIRT1 （pcorr=0.018）和VDR （pcorr=0.009）表达较低。此外，我们观察到SIRT1 mRNA水平与VDR呈正相关（p = 0.01）。这些基因的表达水平与基于心血管反射试验（cart）的评分呈负相关。此外，与野生型等位基因相比，VDR基因中rs2228570的变异等位基因与该基因的高表达相关（p = 0.003）。结论：在DN患者中，SIRT1和VDR表达水平均降低且相互关联。低VDR表达水平会对SIRT1转录产生负面影响，从而影响该蛋白调控的DN的所有主要发病途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Diabetologica 医学-内分泌学与代谢

CiteScore

7.30

自引率

2.60%

发文量

180

审稿时长

2 months

期刊介绍： Acta Diabetologica is a journal that publishes reports of experimental and clinical research on diabetes mellitus and related metabolic diseases. Original contributions on biochemical, physiological, pathophysiological and clinical aspects of research on diabetes and metabolic diseases are welcome. Reports are published in the form of original articles, short communications and letters to the editor. Invited reviews and editorials are also published. A Methodology forum, which publishes contributions on methodological aspects of diabetes in vivo and in vitro, is also available. The Editor-in-chief will be pleased to consider articles describing new techniques (e.g., new transplantation methods, metabolic models), of innovative importance in the field of diabetes/metabolism. Finally, workshop reports are also welcome in Acta Diabetologica.