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 magnetic resonance imaging (MRI) and spectroscopy (MRS), and 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m in-plane resolution 1 H MRI to visualise anatomical skin regions ex vivo from skin biopsies taken intra-operatively, 23 Na 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 co-localizes 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 for high levels of bound sodium within human dermis, co-locating to the GAG scaffold, consistent with a dermal 'third space repository' for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.

Angiotensin-(3–4) normalizes the elevated arterial blood pressure and abnormal Na+/energy handling associated with chronic undernutrition by counteracting the effects mediated by type 1 angiotensin II receptors

“…Here, Na + bound possibly colocalizes with the glycosaminoglycan scaffold as demonstrated in humans [52] and rodents [53]. The responses of Na + balance to the treatments by Losartan and Ang- (3)(4) in CTRL and RBD rats-especially the accentuated negative Na + balance with the combined treatment-lead us to conclude that they rely on the inhibition of the Ang II)AT 1 R axis and the counteracting stimulation by Ang-(3-4) of the Ang II)AT 2 R axis [12].…”

Intercorrelated variability in blood and hemodynamic biomarkers reveals physiological network in hemodialysis patients

“…It has been thought that hyperglycemia and the associated diuresis, glucosuria, and hyperinsulinemia cause upregulation of renal glucose transporters and sodium channels, leading to increased renal sodium reabsorption 64 , 65 . On the other hand, recent studies using 23 Na magnetic resonance imaging have reported that sodium can be stored in the skin in an osmotically inactive form and that this dermal Na-binding capacity is reduced in T2D patients 60 , 66 . Our results indicate that in dialysis patients who have already lost renal function, diabetic patients are still more impaired in sodium regulation than non-diabetic patients.…”

A phantom for the quantitative determination and improvement of the spatial resolution in slice-selective 2D-FT magnetic resonance micro-imaging and -microscopy based on Deep X-ray Lithography (DXRL)

“…Ideal phantoms for standard 2D-FT-MRI should exhibit therefore a strong anisotropy with regard to in-plane lateral distance of the grid bars with reference to their structural height in slice (z-) direction. Usual slice thickness in 2D-FT-microscopy ranges between 50 and 200 μm (see, e.g., [9,12,26]). The demands on the manufacturing technology for offering lateral structures down to 1 μm at height of 50-200 μm, corresponding to aspect ratios of about 50-200 are therefore very challenging.…”

“…MRI with pixel size in that spatial range is therefore called MR-microscopy (MRM) [5]. MR-based histology [6] in the microscopic range has been reported on pathologic structural changes in tissue samples ex-vivo, for arteriosclerosis [7], arthritic changes in cartilage [8], diabetes related changes in the human skin [9] and ovarian cancer [10].…”