title: Salivary gland hypofunction in KK-Aytype 2 diabetic mice.
abstract: BACKGROUND
  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-Aymice as an experimental model of type 2 diabetes.
  
  
  METHODS
  The mechanisms involved in diabetes-induced xerostomia were investigated using the ex vivo glandular perfusion technique, histological analysis, and immunohistochemical and intracellular signaling analyses.
  
  
  RESULTS
  Ex vivo submandibular gland secretions from KK-Aymice decreased by 30% following stimulation with 0.3 μmol/L carbachol (CCh), a cholinergic agonist. Acinar cell weight was comparable between KK-Ayand control mice, whereas duct cell weight was significantly greater in KK-Aymice. Concentrations of Na+and Cl-in the secreted saliva decreased significantly in KK-Aymice, supporting the finding of increased ductal tissue in KK-Aymice. Immunohistochemistry revealed no significant differences between KK-Ayand 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 [Ca2+]iin response to 0.3 μmol/L CCh was reduced by 30% in KK-Aymice, although there was no significant difference in the thapsigargin (1.0 μmol/L)-induced increase in store-depleted calcium between KK-Ayand control mice.
  
  
  CONCLUSIONS
  These results demonstrate that submandibular fluid secretion is diminished in KK-Aymice because of a diminished increase in [Ca2+]i. Duct cell weight increased in KK-Aymice, possibly leading to increased ion reabsorption and thus decreased Na+and Cl-concentrations in the secreted saliva.
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Munemasa
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Mukaibo
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Masaki
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kusuda
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Tsuka
authors.affiliation: Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hosokawa
authors.affiliation: Department of Prosthodontics, Matsumoto Dental University, Nagano, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nakamoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015220:Calcium Channels; D002118:Calcium
keywords: cell signaling; saliva; saliva physiology; 唾液; 唾液生理; 细胞信号传导