Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus
Petra Hanson, Christopher J. Philp, Harpal S. Randeva, Sean James, J. Paul O’Hare, Thomas Meersmann, Galina E. Pavlovskaya, Thomas M. Barber
Petra Hanson, Christopher J. Philp, Harpal S. Randeva, Sean James, J. Paul O’Hare, Thomas Meersmann, Galina E. Pavlovskaya, Thomas M. Barber
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Research Article Endocrinology

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

Abstract

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 μm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na 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.

Authors

Petra Hanson, Christopher J. Philp, Harpal S. Randeva, Sean James, J. Paul O’Hare, Thomas Meersmann, Galina E. Pavlovskaya, Thomas M. Barber

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Figure 3

Illustration of 23Na MRI biopsy.

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Illustration of 23Na MRI biopsy. (A) Photograph of a typical skin sample...
(A) Photograph of a typical skin sample with indication of MRI axial view, left, and a high-resolution 1H MRI slice (11 × 11 × 100 μm3, axial view) showing the anatomy of the DB9 skin sample (right). (B) Histological GAG staining of typical skin specimen (i.e., harvested from NDB8) (left) and histology slice scaled to match the scale of the 1H MRI slice of DB9 to demonstrate that GAGs are localized predominantly in the dermis layer (right). The boundary of the dermis layer is indicated with red line, while blue line reflects the depth of GAG staining determined from histology. (C) Localization of free sodium in DB9 obtained through 23Na MRI (left) and its overlay with skin anatomical 1H MRI slice of DB9 (right). (D) Localization of bound sodium in DB9 obtained through TQF 23Na MRI (left) and its overlay with skin anatomical 1H MRI slice of DB9 (right). Note that free and bound sodium coregister predominantly with the dermis layer where GAGs are located. Sodium concentrations are expressed through the observed 23Na signal/noise ratios (SNRs).