Louchami Karim, Best Len, Brown Peter, Virreira Myrna, Hupkens Emeline, Perret Jason, Devuyst Olivier, Uchida Shinichi, Delporte Christine, Malaisse Willy J, Beauwens Renaud, Sener Abdullah
Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium.
Cell Physiol Biochem. 2012;29(1-2):65-74. doi: 10.1159/000337588. Epub 2012 Mar 1.
BACGROUNS/AIMS: Several insulinotropic agents were recently reported to cause β-cell swelling. The possible participation of AQP7 to water transport was investigated in AQP7(+/+) or AQP7(-/-) mice.
Aquaporin expression, insulin secretion, cell swelling and electrical activity were investigated in pancreatic islets.
RT-PCR revealed the expression of AQP5 and AQP8 mRNA. Double immunofluorescent labeling indicated their presence in β-cells. Whilst basal insulin release from isolated pancreatic islets incubated at 2.8 mM D-glucose did not differ between AQP7(+/+) or AQP7(-/-) mice, the secretion of insulin evoked by the omission of 50 mM NaCl, the substitution of 50 mM NaCl by 100 mM glycerol or a rise in D-glucose concentration to 8.3 mM and 16.7 mM was severely impaired in the islets from AQP7(-/-) mice. Yet, exposure of β-cells to either the hypotonic medium or a rise in D-glucose concentration caused a similar degree of swelling and comparable pattern of electrical activity in cells from AQP7(+/+) and AQP7(-/-) mice. Both the cell swelling and change in membrane potential were only impaired in AQP7(-/-) cells when exposed to 50 mM glycerol.
It is proposed, therefore, that AQP7 may, directly or indirectly, play a role at a distal site in the exocytotic pathway.
背景/目的:最近有报道称几种促胰岛素分泌剂会导致β细胞肿胀。在AQP7(+/+)或AQP7(-/-)小鼠中研究了水通道蛋白7(AQP7)参与水转运的可能性。
对胰岛中的水通道蛋白表达、胰岛素分泌、细胞肿胀和电活动进行了研究。
逆转录聚合酶链反应(RT-PCR)显示了水通道蛋白5(AQP5)和水通道蛋白8(AQP8)信使核糖核酸(mRNA)的表达。双重免疫荧光标记表明它们存在于β细胞中。虽然在2.8 mM D-葡萄糖条件下孵育的分离胰岛中,AQP7(+/+)或AQP7(-/-)小鼠的基础胰岛素释放没有差异,但在AQP7(-/-)小鼠的胰岛中,50 mM氯化钠缺失、50 mM氯化钠被100 mM甘油替代或D-葡萄糖浓度升至8.3 mM和16.7 mM所诱发的胰岛素分泌严重受损。然而,将β细胞暴露于低渗培养基或D-葡萄糖浓度升高时,AQP7(+/+)和AQP7(-/-)小鼠的细胞肿胀程度相似,电活动模式相当。仅当暴露于50 mM甘油时,AQP7(-/-)细胞中的细胞肿胀和膜电位变化才受损。
因此,有人提出AQP7可能直接或间接在胞吐途径的远端位点发挥作用。