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.
Highlights
Established dogma adopted nearly 40 years ago [1] states that urinary sodium output matches dietary sodium intake in normal human physiology
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
Our understanding of human sodium homeostasis has been transformed by insights from data that have emerged from the Mars program, conducted as part of preparation for the prolonged zero-gravity of flights to Mars [2]
Summary
Established dogma adopted nearly 40 years ago [1] states that urinary sodium output matches dietary sodium intake in normal human physiology. For the first time to our knowledge, data from these studies demonstrate, in humans, the existence of ultra-long (including infradian) rhythmic variations in urinary sodium excretion [4] These rhythms occurred despite maintenance of a constant dietary sodium intake [3, 5]. In addition to there being an apparent mismatch between dietary sodium intake and urinary sodium excretion over many days and weeks, another observation was that, for those cosmonauts on a high-sodium diet, there was apparent retention of sodium without associated weight gain [3] This observation is important, as it challenges established dogma that states that, in normal physiology, retention of sodium always associates commensurately with retained water (through osmosis), thereby influencing body weight. 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)
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