Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
Department of Prosthodontics, Matsumoto Dental University, Nagano, Japan.
J Diabetes. 2018 Jan;10(1):18-27. doi: 10.1111/1753-0407.12548. Epub 2017 May 9.
Hypofunction of different organs in the body is associated with diabetes, including in the oral cavity. Diabetes is often associated with xerostomia, but the underlying mechanism is not well characterized. Thus, the mechanisms underlying diabetes-induced xerostomia were investigated in this study in KK-A mice as an experimental model of type 2 diabetes.
The mechanisms involved in diabetes-induced xerostomia were investigated using the ex vivo glandular perfusion technique, histological analysis, and immunohistochemical and intracellular signaling analyses.
Ex vivo submandibular gland secretions from KK-A mice decreased by 30% following stimulation with 0.3 μmol/L carbachol (CCh), a cholinergic agonist. Acinar cell weight was comparable between KK-A and control mice, whereas duct cell weight was significantly greater in KK-A mice. Concentrations of Na and Cl in the secreted saliva decreased significantly in KK-A mice, supporting the finding of increased ductal tissue in KK-A mice. Immunohistochemistry revealed no significant differences between KK-A and control mice in terms of the expression of Cl and water channels, Na -K -2Cl cotransporters, and membrane proteins critical for fluid secretion. Cellular signaling analysis revealed that the increase in [Ca ] in response to 0.3 μmol/L CCh was reduced by 30% in KK-A mice, although there was no significant difference in the thapsigargin (1.0 μmol/L)-induced increase in store-depleted calcium between KK-A and control mice.
These results demonstrate that submandibular fluid secretion is diminished in KK-A mice because of a diminished increase in [Ca ] . Duct cell weight increased in KK-A mice, possibly leading to increased ion reabsorption and thus decreased Na and Cl concentrations in the secreted saliva.
身体不同器官的功能障碍与糖尿病有关，包括口腔。糖尿病常伴有口干，但潜在机制尚未得到很好的描述。因此，本研究以 2 型糖尿病的实验模型 KK-A 小鼠为研究对象，探讨了糖尿病引起的口干的潜在机制。
采用离体腺管灌流技术、组织学分析、免疫组化和细胞内信号分析，研究糖尿病引起的口干的机制。
0.3μmol/L 乙酰胆碱（CCh）刺激时，KK-A 小鼠下颌下腺分泌物减少 30%。KK-A 小鼠和对照组小鼠的腺泡细胞重量相当，但 KK-A 小鼠的导管细胞重量明显增加。KK-A 小鼠分泌唾液中的 Na 和 Cl 浓度显著降低，支持 KK-A 小鼠导管组织增加的发现。免疫组化显示，KK-A 小鼠和对照组小鼠的 Cl 和水通道、Na -K -2Cl 协同转运体以及对流体分泌至关重要的膜蛋白表达无显著差异。细胞信号分析显示，0.3μmol/L CCh 刺激时，KK-A 小鼠[Ca ] 的增加减少了 30%，尽管 KK-A 小鼠和对照组小鼠之间的 1.0μmol/L 毒胡萝卜素（thapsigargin）诱导的钙库耗竭引起的钙增加没有显著差异。
这些结果表明，KK-A 小鼠下颌下腺液体分泌减少是由于[Ca ] 的增加减少所致。KK-A 小鼠的导管细胞重量增加，可能导致离子重吸收增加，从而导致分泌唾液中的 Na 和 Cl 浓度降低。
