Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus
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DOI:
10.1172/jci.insight.145470
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发表时间:
2021-06-22
期刊:
影响因子:
8
通讯作者:
Barber, Thomas M.
Barber, Thomas M.
中科院分区:
医学1区
文献类型:
--
作者:
Hanson, Petra;Philp, Christopher J.;Barber, Thomas M.

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背景资料。长期的膳食钠摄入量与尿钠排泄量不匹配。我们的目标是利用MRI和磁共振波谱(MRS)的三量子过滤(TQF)方法定位和定量人体皮肤内的静电结合钠,并探索2型糖尿病(T2D)患者的真皮钠。方法:我们招募了9名患有T2D的成年参与者和8名无糖尿病病史的正常血糖参与者。所有患者都曾因临床原因接受过截肢或腹部皮肤剥离手术。我们使用20微米平面内分辨率的H-1磁共振成像技术对术中皮肤活检的皮肤解剖区域进行可视化,用Na-23 TQF MRI/MRS研究游离钠和结合钠的分布和定量,并用电感耦合等离子体质谱对选定的皮肤样本中的钠进行定量。结果:人真皮中结合钠的优势(>90%)是与糖胺多聚糖(GAG)支架共定位的。结合钠和游离钠具有相似的解剖位置。T2D与皮肤结合钠容量严重降低有关。结论:我们提供了我们所知的人类真皮内高水平结合钠的第一证据,与真皮钠的第三空间储存库相一致。T2D与皮肤对钠的静电结合能力降低有关。
BACKGROUND. Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum-filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D).METHODS. We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 mu m in-plane resolution H-1 MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, Na-23 TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples.RESULTS. Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity.CONCLUSION. We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.