title: Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver.
abstract: Aquaglyceroporins form the subset of the aquaporin water channel family that is permeable to glycerol and certain small, uncharged solutes. AQP9 has unusually broad solute permeability and is expressed in hepatocyte plasma membranes. Proteoliposomes reconstituted with expressed, purified rat AQP9 protein were compared with simple liposomes for solute permeability. At pH 7.5, AQP9 proteoliposomes exhibited Hg(2+)-inhibitable glycerol and urea permeabilities that were increased 63-fold and 90-fold over background. beta-Hydroxybutyrate permeability was not increased above background, and osmotic water permeability was only minimally elevated. During starvation, the liver takes up glycerol for gluconeogenesis. Expression of AQP9 in liver was induced up to 20-fold in rats fasted for 24-96 h, and the AQP9 level gradually declined after refeeding. No changes in liver AQP9 levels were observed in rats fed ketogenic diets or high-protein diets, but AQP9 levels were elevated in livers of rats made diabetic by streptozotocin injection. When blood glucose levels of the diabetic rats were restored to normal by insulin treatments, the AQP9 levels returned to baseline. Confocal immunofluorescence revealed AQP9 immunostaining on the sinusoidal surfaces of hepatocyte plates throughout the livers of control rats. Denser immunostaining was observed in the same distribution in livers of fasted and streptozotocin-treated rats. We conclude that AQP9 serves as membrane channel in hepatocytes for glycerol and urea at physiological pH, but not for beta-hydroxybutyrate. In addition, levels of AQP9 expression fluctuate depending on the nutritional status of the subject and the circulating insulin levels.
authors.affiliation: Department of Biological Chemistry and Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Carbrey
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gorelick-Feldman
authors.forename: David
authors.initials: D
authors.lastname: Kozono
authors.forename: Jeppe
authors.initials: J
authors.lastname: Praetorius
authors.forename: Soren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Peter
authors.initials: P
authors.lastname: Agre
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020346:Aquaporins / Q000378:metabolism* / Q000502:physiology*; D001786:Blood Glucose; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005990:Glycerol / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009865:Oocytes / Q000378:metabolism; D010539:Permeability; D010957:Plasmids / Q000378:metabolism; D021381:Protein Transport; D011510:Proteolipids / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors; D014508:Urea / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000900:Anti-Bacterial Agents; C491637:Aqp9 protein, rat; D020346:Aquaporins; D001786:Blood Glucose; D007328:Insulin; D011510:Proteolipids; D018075:RNA, Complementary; C020485:proteoliposomes; D013311:Streptozocin; D014508:Urea; D005990:Glycerol; D020155:3-Hydroxybutyric Acid