Dysfunction of the salivary gland in NOD mouse

NOD小鼠唾液腺功能障碍

• 批准号: 07672199
• 负责人: NAKAGAWA Yoichi
• 金额: $ 1.47万
• 依托单位: Tsurumi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672199/
• 关键词: Sjogren's syndrome; NOD mouse; salivary gland; signal transduction; neuropeptide; Insulin-like growth factor; 唾液腺機能; 自己免疫疾患; 糖尿病; Insulin-like Growth Factor; IGF-binding protein; 組織内濃度; ムスカリン受容体; cAMP; イノシトール; 自己抗体

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

非肥胖糖尿病(NOD)小鼠已被公认为1型胰岛素依赖型自身免疫性糖尿病的动物模型，并已显示唾液腺分泌功能丧失。为了解NOD小鼠唾液腺功能的变化，进行了以下几个方面的研究：(1)对M受体刺激的分泌反应：NOD显示腺体产生cAMP的能力降低。NOD小鼠颌下腺基础和激动剂刺激下的肌醇磷酸浓度均降低。腺体内受体密度降低。毒鼠碱激动剂反应的减少被认为是由于检测到针对细胞表面抗原的自身抗体导致信号转导成分的普遍减少。(2)神经肽和唾液腺反应的水平：注射三种神经肽之一，P物质(SP)，血管活性肠多肽…More(VIP)和神经肽Y(NPY)与毒扁豆碱能激动剂匹罗卡品联合应用可增加Balb/c小鼠的唾液流率，而对NOD小鼠的唾液流率没有明显的增加作用。放射免疫测定法测定颌下腺和腮腺中神经肽的浓度显示，随着糖尿病的发病，SP水平降低。NOD组小鼠颌下腺VIP含量降低。结果提示，NOD小鼠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，但在唾液中检测不到。灌胃给药的放射性标记的IGF显示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，这表明这可能是导致生长和伤口愈合能力下降的原因。较少

项目成果

Yamamoto, H., Ishibashi, K., Nakagawa, Y., Maeda, N., Zeng, T., Robinson, C.P., Oxford, g.E., Chegini, N.and Humphreys-Beher, M.G.: "Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model

Yamamoto, H.、Ishibashi, K.、Nakakawa, Y.、Maeda, N.、Zeng, T.、Robinson, C.P.、Oxford, g.E.、Chegini, N. 和 Humphreys-Beher, M.G.：“检测

YAMAMOTO,H: "Alterations in the secretory response of Non-obese diabetic (NOD) mice to muscarinic receptor stimulation" Clinical Immunology and Immunopathology. 78・3. 245-255 (1996)

YAMAMOTO, H：“非肥胖糖尿病 (NOD) 小鼠对毒蕈碱受体刺激的分泌反应的改变”临床免疫学和免疫病理学 78·3 (1996)。

Yamamoto, H., et al.: "Alteration in the secretory response of non-obese diabetic(NOD)mice to muscarinic receptor stimulation." Clinical Immunology and Immunopathology. 78(3). 245-255 (1996)

Yamamoto, H. 等人：“非肥胖糖尿病 (NOD) 小鼠对毒蕈碱受体刺激的分泌反应的改变。”

Yamamoto, H., Sims, E.S., Macauley, S.P., Nguyen, K-H.T., Nakagawa, Y.and Humphreys-Beher, M.G.: "Alteration in the secretory response of non-obese diabetic (NOD) mice to muscarinic receptor stimulation." Clinical Immunology and Immunopathology. 78(3). 24

Yamamoto, H.、Sims, E.S.、Macauley, S.P.、Nguyen, K-H.T.、Nakakawa, Y. 和 Humphreys-Beher, M.G.：“非肥胖糖尿病 (NOD) 小鼠对毒蕈碱受体刺激的分泌反应的改变

Yamamoto, H., et al.: "Detection of alterations in the levels of neuropeptides and salivary gland responses in the non-obese diabetic mouse model for autoimmune sialoadenitis." Scand J immunol. 45. 55-61 (1997)

Yamamoto, H. 等人：“检测自身免疫性唾液腺炎的非肥胖糖尿病小鼠模型中神经肽水平和唾液腺反应的变化。”