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2 型糖尿病患者的血管生成 T 细胞减少,并被二肽基肽酶-4 抑制剂利拉利汀募集:一项随机、安慰剂对照试验(RELEASE 研究)的亚分析。

Angiogenic T cells are decreased in people with type 2 diabetes mellitus and recruited by the dipeptidyl peptidase-4 inhibitor Linagliptin: A subanalysis from a randomized, placebo-controlled trial (RELEASE study).

机构信息

Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

出版信息

Diabetes Obes Metab. 2020 Jul;22(7):1220-1225. doi: 10.1111/dom.14024. Epub 2020 Mar 27.

Abstract

Angiogenic T (Tang) cells are mediators of vascular repair, and are characterized by surface expression of CXCR4. This receptor for stromal cell-derived factor-1α (SDF-1α) is cleaved by dipeptidyl peptidase-4 (DPP-4). Tang cell levels were investigated in people with type 2 diabetes mellitus (T2DM) compared with matched healthy controls and after treatment with the DPP-4 inhibitor Linagliptin. People with T2DM were randomized to 5 mg/day Linagliptin (n = 20) or placebo (n = 21) for 26 weeks. Tang cell frequency was identified in peripheral blood mononuclear cells (CD3 CD31 CXCR4 ) and levels of endothelial progenitor cells (EPCs) (CD34 CD133 KDR ) were also assessed in whole blood. Circulating Tang cell levels were significantly lower in people with T2DM compared with the healthy control group. SDF-1α levels increased significantly in Linagliptin-treated people with T2DM compared to placebo, and a trend was observed in change of Tang cell levels, while EPC count did not change. In conclusion, circulating Tang cell levels were considerably lower in people with T2DM, while a trend was observed in recruitment of Tang cells after 26 weeks of treatment with Linagliptin. These data suggest that DPP-4 inhibitors may potentially exert beneficial effects on bone marrow-driven vascular repair.

摘要

血管生成 T(Tang)细胞是血管修复的介质,其特征在于表面表达 CXCR4。基质细胞衍生因子-1α(SDF-1α)的这种受体可被二肽基肽酶-4(DPP-4)切割。与匹配的健康对照组相比,研究了 2 型糖尿病(T2DM)患者中的 Tang 细胞水平,并在接受 DPP-4 抑制剂利拉利汀治疗后进行了研究。将 T2DM 患者随机分为每天 5 毫克利拉利汀(n = 20)或安慰剂(n = 21)治疗 26 周。在外周血单核细胞(CD3 CD31 CXCR4)中鉴定 Tang 细胞频率,并在全血中评估内皮祖细胞(EPC)的水平(CD34 CD133 KDR)。与健康对照组相比,T2DM 患者的循环 Tang 细胞水平显着降低。与安慰剂相比,接受利拉利汀治疗的 T2DM 患者的 SDF-1α水平显着升高,并且观察到 Tang 细胞水平的变化趋势,而 EPC 计数没有变化。总之,T2DM 患者的循环 Tang 细胞水平明显降低,而接受利拉利汀治疗 26 周后,Tang 细胞的募集趋势明显。这些数据表明,DPP-4 抑制剂可能对骨髓驱动的血管修复具有潜在的有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ec/7317866/d5399ad03491/DOM-22-1220-g001.jpg

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