title: Functional characterization of human aquaporin 9 as a facilitative glycerol carrier.
abstract: The mechanism of glycerol transport by human aquaporin 9 (hAQP9), which is a liver-specific AQP water channel and can also transport glycerol, was investigated by using the Xenopus laevis oocyte expression system. It was found that specific glycerol uptake by hAQP9 was concentration-dependent (saturable) at 25 degrees C, conforming to the Michaelis-Menten kinetics with the maximum transport rate (J(max)) of 0.84 pmol/min/oocyte and the Michaelis constant (K(m)) of 9.2 microM, and temperature-dependent, being reduced by about 70% when temperature was lowered from 25 degrees C to 4 degrees C. Such dependences on concentration and temperature are characteristic of a carrier-mediated type of mechanism rather than a channel type, which is expected not to depend on them. Furthermore, several glycerol-related compounds, such as monoacetin, were found to specifically inhibit hAQP9-mediated glycerol uptake, indicating a possibility of competition with glycerol. hAQP9-mediated glycerol uptake was, however, found not to require Na+. All these results suggest that hAQP9 functions as a facilitative carrier for glycerol, although it had been believed to function as a channel. Findings in the present study provide novel insight into its glycerol-transporting mechanism and would help exploring a possibility that hAQP9 inhibitors might help lower blood glucose level by reducing gluconeogenesis by limiting hepatic glycerol uptake.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Ohgusu
authors.forename: Kin-ya
authors.initials: KY
authors.lastname: Ohta
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Katano
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Urano
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yuasa