{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:45:53Z","timestamp":1790952353639,"version":"4.1.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>In mammals, glycogen synthase kinase (GSK)3 comprises GSK3\u03b1 and GSK3\u03b2 isoforms. GSK3\u03b2 has been shown to play a role in the ability of kidneys to concentrate urine by regulating vasopressin-mediated water permeability of collecting ducts, whereas the role of GSK3\u03b1 has yet to be discerned. To investigate the role of GSK3\u03b1 in urine concentration, we compared GSK3\u03b1 knockout (GSK3\u03b1KO) mice with wild-type (WT) littermates. Under normal conditions, GSK3\u03b1KO mice had higher water intake and urine output. GSK3\u03b1KO mice also showed reduced urine osmolality and aquaporin-2 levels but higher urinary vasopressin. When water deprived, they failed to concentrate their urine to the same level as WT littermates. The addition of 1-desamino-8-d-arginine vasopressin to isolated inner medullary collecting ducts increased the cAMP response in WT mice, but this response was reduced in GSK3\u03b1KO mice, suggesting reduced responsiveness to vasopressin. Gene silencing of GSK3\u03b1 in mpkCCD cells also reduced forskolin-induced aquaporin-2 expression. When treated with LiCl, an isoform nonselective inhibitor of GSK3 and known inducer of polyuria, WT mice developed significant polyuria within 6 days. However, in GSK3\u03b1KO mice, the polyuric response was markedly reduced. This study demonstrates, for the first time, that GSK3\u03b1 could play a crucial role in renal urine concentration and suggest that GSK3\u03b1 might be one of the initial targets of Li<jats:sup>+<\/jats:sup>in LiCl-induced nephrogenic diabetes insipidus.<\/jats:p>","DOI":"10.1152\/ajprenal.00516.2014","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T04:50:40Z","timestamp":1421902240000},"page":"F650-F660","source":"Crossref","is-referenced-by-count":33,"title":["Glycogen synthase kinase 3\u03b1 regulates urine concentrating mechanism in mice"],"prefix":"10.1152","volume":"308","author":[{"given":"Rikke","family":"N\u00f8rregaard","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixin","family":"Tao","sequence":"additional","affiliation":[{"name":"The Kidney Institute, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Woodgett","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayakumar","family":"Kakade","sequence":"additional","affiliation":[{"name":"The Kidney Institute, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S. 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