Eliane F E Wenstedt1, Jetta J Oppelaar1, Stijn Besseling1, Nienke M G Rorije1, Rik H G Olde Engberink1, Arie Oosterhof2, Toin H van Kuppevelt2, Bert-Jan H van den Born3, Jan Aten4, Liffert Vogt5,6. 1. Department of Internal Medicine, Section of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. 2. Department of Biochemistry, Radboud UMC, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands. 3. Department of Internal Medicine, Section of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. 4. Department of Pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. 5. Department of Internal Medicine, Section of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. l.vogt@amsterdamumc.nl. 6. Department of Internal Medicine, Section of Nephrology, Amsterdam UMC, Room D3-324, Meibergdreef 9, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. l.vogt@amsterdamumc.nl.
Abstract
BACKGROUND: By binding to negatively charged polysaccharides called glycosaminoglycans, sodium can be stored in the body-particularly in the skin-without concurrent water retention. Concordantly, individuals with changed glycosaminoglycan structure (e.g. type 1 diabetes (DM1) and hereditary multiple exostosis (HME) patients) may have altered sodium and water homeostasis. METHODS: We investigated responses to acute (30-min infusion) and chronic (1-week diet) sodium loading in 8 DM1 patients and 7 HME patients in comparison to 12 healthy controls. Blood samples, urine samples, and skin biopsies were taken to investigate glycosaminoglycan sulfation patterns and both systemic and cellular osmoregulatory responses. RESULTS:Hypertonic sodium infusion increased plasma sodium in all groups, but more in DM1 patients than in controls. High sodium diet increased expression of nuclear factor of activated t-cells 5 (NFAT5)-a transcription factor responsive to changes in osmolarity-and moderately sulfated heparan sulfate in skin of healthy controls. In HME patients, skin dermatan sulfate, rather than heparan sulfate, increased in response to high sodium diet, while in DM1 patients, no changes were observed. CONCLUSION: DM1 and HME patients show distinct osmoregulatory responses to sodium loading when comparing to controls with indications for reduced sodium storage capacity in DM1 patients, suggesting that intact glycosaminoglycan biosynthesis is important in sodium and water homeostasis. Trial registration These trials were registered with the Netherlands trial register with registration numbers: NTR4095 ( https://www.trialregister.nl/trial/3933 at 2013-07-29) and NTR4788 ( https://www.trialregister.nl/trial/4645 at 2014-09-12).
RCT Entities:
BACKGROUND: By binding to negatively charged polysaccharides called glycosaminoglycans, sodium can be stored in the body-particularly in the skin-without concurrent water retention. Concordantly, individuals with changed glycosaminoglycan structure (e.g. type 1 diabetes (DM1) and hereditary multiple exostosis (HME) patients) may have altered sodium and water homeostasis. METHODS: We investigated responses to acute (30-min infusion) and chronic (1-week diet) sodium loading in 8 DM1patients and 7 HME patients in comparison to 12 healthy controls. Blood samples, urine samples, and skin biopsies were taken to investigate glycosaminoglycan sulfation patterns and both systemic and cellular osmoregulatory responses. RESULTS:Hypertonicsodium infusion increased plasma sodium in all groups, but more in DM1patients than in controls. High sodium diet increased expression of nuclear factor of activated t-cells 5 (NFAT5)-a transcription factor responsive to changes in osmolarity-and moderately sulfated heparan sulfate in skin of healthy controls. In HME patients, skin dermatan sulfate, rather than heparan sulfate, increased in response to high sodium diet, while in DM1patients, no changes were observed. CONCLUSION:DM1 and HME patients show distinct osmoregulatory responses to sodium loading when comparing to controls with indications for reduced sodium storage capacity in DM1patients, suggesting that intact glycosaminoglycan biosynthesis is important in sodium and water homeostasis. Trial registration These trials were registered with the Netherlands trial register with registration numbers: NTR4095 ( https://www.trialregister.nl/trial/3933 at 2013-07-29) and NTR4788 ( https://www.trialregister.nl/trial/4645 at 2014-09-12).
Entities:
Keywords:
Glycosaminoglycan; Hereditary multiple exostoses; Nuclear factor of activated T-cells 5; Osmoregulation; Sodium; Type 1 diabetes
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