Mechanism underlying impaired compartmentalization of AQP5 in parotid glands of diabetic rats and curative drug.

不服用干性药物的糖尿病患者常出现口干症状、口干症。然而，尚不清楚水通道蛋白-5 （AQP5）是否在糖尿病大鼠唾液腺细胞中受到调节运输。在本研究中，我们研究了在毒菌碱激动剂西维美林刺激下，正常和链脲佐菌素诱导的糖尿病大鼠腮腺中AQP5亚细胞定位的差异。西维米林诱导对照大鼠腮腺细胞顶质膜（APM）中AQP5的数量增加，而糖尿病大鼠则无此作用。免疫组织化学研究表明，在非刺激条件下，AQP5荧光与flotilin -2和GM1荧光在对照组和糖尿病大鼠腮腺细胞质中均呈弥漫性共定位。静脉注射西维美林10 min后，AQP5荧光与flotilin -2、GM1荧光显著升高，对照组大鼠的rotid细胞增多，糖尿病大鼠的rotid细胞增多。注射后60分钟，对照大鼠细胞质中出现弥漫性荧光。糖尿病大鼠腮腺细胞中AQP5的总量没有明显减少，但细胞中AQP5 mRNA的数量明显增加。在对照大鼠中观察到，给糖尿病大鼠注射胰岛素后，西维梅林诱导的AQP5通过脂筏运输到腮腺细胞的APM，细胞中AQP5 mRNA的数量恢复。这些发现表明，大鼠腮腺细胞中AQP5的合成不受糖尿病的影响，而是受转录的影响。用西维美林处理腮腺组织10分钟后，对照组大鼠的AQP5溶解度降低1% Triton X-100，但糖尿病大鼠的AQP5溶解度没有下降，这表明在脂筏运输到APM后，AQP5在腮腺细胞的APM中从脂筏解离到非筏。结果表明，在毒菌碱激动剂作用下，唾液腺细胞中AQP5与脂筏向APM的易位受损导致糖尿病性口干症。少

Patients with diabetes mellitus who do not take xerogenic drugs often complain of dry-mouth symptoms, xerostomia. It remains unknown, however, whether aquaporin-5 (AQP5) is subjected to regulated trafficking in salivary gland cells of diabetic rats. In this study, we investigated the difference of subcellular localization of AQP5 in parotid glands of control and streptozocin-induced diabetic (diabetic) rats stimulated by the muscarinic agonist, cevimeline. Cevimeline induced an increase in the amount of AQP5 in the apical plasma membrane (APM) in parotid cells of control rats, but not diabetic rats. Immunohistochemical study indicated that AQP5 fluorescence, under unstimulated conditions, was colocalized with flotillin-2 and GM1 fluorescence in a diffuse pattern in the parotid cytoplasm of both control and diabetic rats. Ten minutes after intravenous injection of cevimeline, AQP5 fluorescence was dramatically increased together with flotillin-2 and GM1 fluorescence in the APM of the pa … More rotid cells of control rats, but not diabetic rats. Sixty minutes after the injection, there was diffuse pattern of fluorescence in the cytoplasm of control rats. The total amount of AQP5 did not decrease significantly in parotid cells of diabetic rats, but there was a significant increase in the amount of AQP5 mRNA in these cells. Administration of insulin to diabetic rats produced the cevimeline-induced trafficking of AQP5 with lipid rafts to the APM in parotid cells and the recovery of the amount of AQP5 mRNA in the cells, as observed in control rats. These findings indicate that AQP5 synthesis in rat parotid cells is not affected by diabetes mellitus at the translation step, but rather at the transcription step. Treatment of the parotid tissues with cevimeline for 10 min induced a decrease in the solubility of AQP5 by 1 % Triton X-100 in control rats, but not in diabetic rats, indicating that after trafficking with lipid rafts to the APM, AQP5 dissociates from lipid rafts to non-rafts in the APM in parotid cells. The results suggest that the impaired AQP5 translocation with lipid rafts to the APM in salivary gland cells in response to muscarinic agonists results in diabetic xerostomia. Less