Department of Morphological Biology, Fukuoka Dental College, Tamura, Sawara-ku, Japan.
Arch Oral Biol. 2010 Nov;55(11):848-54. doi: 10.1016/j.archoralbio.2010.07.015. Epub 2010 Aug 21.
A genetically diabetic mouse strain (db/db) exhibits severe obesity and a syndrome resembling human non-insulin-dependent diabetes mellitus. Our histological study of submandibular glands revealed that the size and area of the granular convoluted tubules was substantially decreased in db/db mice. We hypothesized that this structural difference reflected a specific alteration in salivary duct function.
The saliva evoked by pilocarpine was used for the measurement of ion concentrations, and submandibular glands were dissected out for the immunohistochemistry and real-time PCR study.
The K(+) concentration of the salivary secretion was higher in db/db than in control m+/m+ mice, while neither saliva volume nor the concentrations of Na(+) or Cl⁻ differed between these strains. In db/db mice (vs. m+/m+ mice): quantitative PCR analysis revealed an increased mRNA expression of large-conductance Ca²(+)-activated K(+) (maxi-K) channels, immunohistochemistry revealed an increase in the luminal surface expression of the maxi-K channel protein, and a particularly interesting finding was that there was a substantial increase in the salivary tissue-specific splice variant ParSlo.
These results suggest that in db/db mice, the K(+) content of saliva may be elevated due to an expression of a maxi-K channel variant, which results from a modification of ductal structure.
Our data may shed some light on the mechanism responsible for determining the dynamics of salivary K(+) concentration increased in diabetic patients.
一种遗传性糖尿病小鼠品系(db/db)表现出严重肥胖和类似于人类非胰岛素依赖型糖尿病的综合征。我们对颌下腺的组织学研究表明,db/db 小鼠的颗粒曲管的大小和面积显著减小。我们假设这种结构差异反映了唾液管功能的特定改变。
用毛果芸香碱诱发唾液,用于测量离子浓度,并分离颌下腺进行免疫组织化学和实时 PCR 研究。
db/db 小鼠的唾液分泌中 K+浓度高于对照 m+/m+小鼠,而两种品系的唾液量和 Na+或 Cl-浓度均无差异。在 db/db 小鼠(与 m+/m+小鼠相比):定量 PCR 分析显示大电导 Ca2+激活 K+(maxi-K)通道的 mRNA 表达增加,免疫组织化学显示 maxi-K 通道蛋白的管腔表面表达增加,一个特别有趣的发现是,唾液组织特异性剪接变体 ParSlo 的表达显著增加。
这些结果表明,在 db/db 小鼠中,由于 maxi-K 通道变体的表达,唾液中的 K+含量可能升高,这是由于导管结构的改变所致。
我们的数据可能为确定糖尿病患者唾液中 K+浓度增加的动力学机制提供一些线索。