Dysfunction of the salivary gland in NOD mouse

非肥胖糖尿病（NOD）小鼠已被认为是自身免疫性1型胰岛素依赖型糖尿病的动物模型，并且已显示唾液腺分泌功能的丧失。为了了解NOD小鼠唾液腺功能的变化，进行了以下研究。(1)对毒蕈碱受体刺激的分泌反应：NOD显示腺体中cAMP生成的潜力降低。NOD小鼠的下颌下腺中磷酸肌醇的基础和激动剂刺激浓度降低。腺体内受体密度降低。毒蕈碱激动剂反应的减少被认为是由于信号转导成分的普遍减少，作为检测到的针对细胞表面抗原的自身抗体的结果。(2)神经肽水平与唾液腺反应：注射P物质（SP）、血管活性肠肽（VIP）、 ...更多信息 (VIP)和神经肽Y（NPY）与毒蕈碱胆碱能激动剂毛果芸香碱联合使用可增加Balb/c小鼠的唾液流速，而对NOD小鼠的流速没有观察到增加。放射免疫测定法测定的神经肽浓度在下颌下腺和腮腺显示降低水平的SP糖尿病发病。NOD小鼠的下颌下腺中VIP浓度降低。研究结果表明，NOD小鼠中观察到的功能障碍是由于唾液腺细胞部分神经递质反应性的普遍丧失。(3)胃肠道对胰岛素样生长因子（IGF）的吸收和胰岛素样生长因子结合蛋白（IGFBP）的水平在血清中检测到，但在唾液中未检测到。放射性标记IGF的灌胃给药表明从胃肠道大量摄取和显著的组织分布。糖尿病NOD小鼠中的组织分布减少，这表明有助于降低生长和伤口愈合潜力。少

The non-obese diabetic (NOD) mouse has been recognized as an animal model for autoimmune type 1 insulin-dependent diabetes mellitus and has been shown a loss in secretory function of the salivary glands. To understand the salivary functional changes of the salivary gland in NOD mouse, the following investigations were carried out.(1) The secretory response to muscarinic receptor stimulation : NOD showed a reduced potential for the generation of cAMP in the glands. Basal and agonist stimulated concentrations of inositol phosphate were reduced in submandibular gland of NOD mice. The receptor density was decreased in the glands. The reduction of muscarinic agonist response was suggested to be due to a generalized reduction in signal transduction components as a consequence of autoantibodies detected against cell surface antigens.(2) The levels of neuropeptides and salivary gland responses : Injection of either of the three neuropeptides, substance P (SP), vasoactive intestinal polypeptide … More (VIP), and neuropeptide Y (NPY), in combination with the muscarinicchorinergic agonist pilocarpine increased saliva flow rates in Balb/c mice while threr was no observable augmentation to flow rates in NOD mice. Radioimmunoassay determination of neuropeptide concentrations in the submandibular and parotid glands revealed reduced levels of SP with diabetic onset. VIP concentrations were reduced in the submandibular gland of NOD mice. The findings suggested the dysfunction observed in NOD mice to be due to a general loss of neurotransmitter responsiveness on the part of salivary gland cells.(3) Gastrointestinal absorption of Insulin-like growth factor (IGF) and the levels of Insulin-like growth factor binding protein (IGFBP) : IGFBP were detected in the sera, but not in the saliva. Gavage administration of radiolabeled IGF indicated substantial uptake from the gastrointestinal tract and significant tissue distribution. The tissue distribution in the diabetic NOD mouse was reduced, which suggest to contribute to reduced growth and wound healing potentials. Less