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Fructose Driven Vasopressin (VP) Secretion May Contribute to Chronic Kidney Diseases (CKD) under Chronic Dehydration
Author(s) -
Song Zhilin,
Garcia Miguel,
Roncal Carlos
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.658.7
Subject(s) - copeptin , medicine , endocrinology , vasopressin , chemistry , secretion
Chronic recurrent dehydration (WAN) can cause CKD, through a fructokinase (KHK) dependent way. VP is a peptide hormone that is synthesized in the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), and is subsequently transported to and stored in posterior pituitary (PP), from where it is released into systemic circulation. VP may mediate some types of CKD through currently unclear mechanisms. Here we propose a novel mechanism for CKD resulted from chronic dehydration, that chronic dehydration may activate a local polyol pathway: aldose reductase (AR)‐fructose‐KHK, leading to elevated VP and thus worsening CKD. Current studies have shown existence of KHK mRNA in hypothalamic area and expression of KHK protein in both SON and PVN. The rise of copeptin, a serum marker of VP, was observed in wild type (WT)/WAN mice, but not in KHK‐KO/WAN mice. Further analysis revealed that VP storage in PP was elevated in WT/WAN mice compared with control WT mice, but was greatly reduced to about control level in KHK‐KO/WAN mice. KHK‐KO did not significantly affect VP storage in PP or serum copeptin levels in control mice. These results demonstrate that chronic dehydration may lead to CKD, at least partially, through elevated VP synthesis and secretion driven by activation of the AR‐fructose‐KHK polyol pathway. Future studies will further clarify the underlying mechanisms.