Liu Shuai-Nan, Liu Quan, Shen Zhu-Fang
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Yao Xue Xue Bao. 2008 Nov;43(11):1106-11.
This study is to evaluate beta cell function and investigate the mechanism of impaired pancreatic islet beta cell function in monosodium glutamate (MSG) obese rat with insulin resistance, an animal model of metabolic syndrome. Insulin tolerance test was used to screen MSG obese rats with insulin resistance. Blood concentrations of glucose, triglyceride, total cholesterol and insulin were determined. Beta cell function was assessed with hyperglycemic clamp technique. The morphological alterations in pancreas and changes of islet beta cell mass were evaluated by hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining. Lipid, oxidative stress relevant factors, nitric oxide (NO) level and activity of ATPase in pancreas and pancreatic mitochondrial were tested. The MSG obese rats with insulin resistance could be validated as a typical metabolic syndrome animal model possessing increased fasting plasma triglycerides and insulin (P < 0. 001), markedly decreased weight indices of pancreas and impaired glucose-stimulated insulin secretion. Hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining showed increased adipocytes and fibroplasia deposition in pancreas and reduced beta cell mass. The increased contents of triglyceride and NO level, the decreased SOD levels and activities of total ATPase (P < 0.001), Na+-K+-ATPase (P < 0.001) and Ca2+-Mg2+-ATPase (P < 0.01) were observed in pancreas and its mitochondria versus normal rat. The study demonstrates that accumulation of lipids in pancreas could lead to increased systemic indicators of inflammation, such as NO, which may influence the activities of several kinds of ATPase in cell membranes and interfere the ion transport, substance metabolism and energy production in pancreas. Finally the MSG obese rats characterized with metabolic syndrome displayed an impairment of beta cell function.
本研究旨在评估β细胞功能，并探讨胰岛素抵抗的味精（MSG）肥胖大鼠（一种代谢综合征动物模型）胰岛β细胞功能受损的机制。采用胰岛素耐量试验筛选胰岛素抵抗的MSG肥胖大鼠。测定血糖、甘油三酯、总胆固醇和胰岛素的血药浓度。用高血糖钳夹技术评估β细胞功能。通过苏木精-伊红（HE）染色和Gomori醛复红染色评估胰腺的形态学改变和胰岛β细胞量的变化。检测胰腺和胰腺线粒体中的脂质、氧化应激相关因子、一氧化氮（NO）水平和ATP酶活性。胰岛素抵抗的MSG肥胖大鼠可被确认为典型的代谢综合征动物模型，其空腹血浆甘油三酯和胰岛素水平升高（P<0.001），胰腺重量指数显著降低，葡萄糖刺激的胰岛素分泌受损。苏木精-伊红（HE）染色和Gomori醛复红染色显示胰腺中脂肪细胞增多和成纤维细胞沉积增加，β细胞量减少。与正常大鼠相比，胰腺及其线粒体中甘油三酯含量增加、NO水平升高、超氧化物歧化酶（SOD）水平和总ATP酶（P<0.001）、钠钾ATP酶（P<0.001）及钙镁ATP酶（P<0.01）活性降低。该研究表明，胰腺中脂质的积累可导致全身炎症指标升高，如NO，这可能影响细胞膜中几种ATP酶的活性，干扰胰腺中的离子转运、物质代谢和能量产生。最后，具有代谢综合征特征的MSG肥胖大鼠表现出β细胞功能受损。
