title: Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.
abstract: Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired.
  
  
  
  This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado; Zhilin.song@ucdenver.edu.|Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Song 宋志林
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal-Jimenez
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa-Garcia
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Oppelt
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Masanari
authors.initials: M
authors.lastname: Kuwabara
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.|Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Tamara
authors.initials: T
authors.lastname: Milagres
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Ana
authors.initials: A
authors.lastname: Andres-Hernando
authors.affiliation: Departments of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan; and.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Garcia
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Ginger
authors.initials: G
authors.lastname: Johnson
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Paul S
authors.initials: PS
authors.lastname: MacLean
authors.affiliation: Laboratory of Renal Physiopathology, INC Ignacio Chávez, Mexico City, Mexico.
authors.forename: Laura-Gabriela
authors.initials: LG
authors.lastname: Sanchez-Lozada
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts.
authors.forename: Dean R
authors.initials: DR
authors.lastname: Tolan
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003681:Dehydration / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005631:Fructokinases / Q000172:deficiency* / Q000235:genetics; D005632:Fructose / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006358:Hot Temperature / Q000009:adverse effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism*; D014868:Water Deprivation
chemical_list: D012333:RNA, Messenger; D014667:Vasopressins; D005632:Fructose; D005631:Fructokinases; C046173:fructokinase
keywords: aldose reductase; dehydration; fructokinase; fructose; uric acid; vasopressin