Dysfunction of the salivary gland in NOD mouse

非肥胖型糖尿病（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，并已显示唾液腺分泌功能丧失。为了了解NOD小鼠唾液腺功能的变化，我们进行了以下研究。(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。基础和激动剂刺激的肌醇磷酸浓度在NOD小鼠颌下腺中降低。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，这是检测到针对细胞表面抗原的自身抗体的结果。(2)神经肽水平和唾液腺反应：注射P物质（SP）、血管活性肠多肽（VIP）和神经肽Y （NPY）中的任何一种神经肽，联合肌碱胆碱能激动剂匹罗卡平，可增加Balb/c小鼠的唾液流速，而对NOD小鼠的唾液流速没有明显的增加。放射免疫法测定下颌下腺和腮腺的神经肽浓度显示，SP水平随糖尿病发作而降低。NOD小鼠颌下腺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神经递质反应性的普遍丧失。(3)胃肠道胰岛素样生长因子（IGF）吸收及胰岛素样生长因子结合蛋白（IGFBP）水平：血清中检测到IGFBP，唾液中未检测到IGFBP。放射性标记的IGF灌胃显示从胃肠道大量摄取和显著的组织分布。糖尿病NOD小鼠的组织分布减少，这可能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