急性高血糖影响小鼠第一时相胰岛素分泌的机制

发布时间：2018-10-15 12:16

【摘要】：目的观察急性高血糖影响小鼠第一时相胰岛素分泌的功能及形态学变化特点。方法给C57/BL 6J小鼠完成颈静脉插管后输注20%高糖溶液4 h,建立急性糖毒性小鼠模型,行腹腔葡萄糖耐量实验(intraperitoneal glucose tolerance test,IPGTT)及口服葡萄糖耐量实验(oral glucose tolerance test,OGTT)评价葡萄糖耐量及胰岛素分泌功能。HE染色及电镜观察胰岛形态变化及细胞内胰岛素分泌颗粒亚细胞结构变化。结果 IPGTT实验中急性糖毒性组15 min血糖值较对照组显著增加[(10.3±0.33)mmol/L vs(19.3±1.66)mmol/L],上升87%(P0.05),OGTT实验中30 min血糖值较对照组显著增加[(9.8±0.31)mmol/L vs(18.16±1.01)mmol/L],升高85%(P0.05),且早期胰岛素分泌高峰受损且分泌延迟。GSIS实验中急性糖毒性组在基础状态时(葡萄糖浓度2.8 mmol/L)和高糖(16.7 mmol/L)刺激后,胰岛素分泌较对照组显著降低[(0.481±0.003)ng/m L vs(0.702±0.121)ng/m L,(2.43±0.03)ng/m L vs(4.07±0.34)ng/m L],分别下降46%和67%(P0.05);胰岛素含量测定结果显示,急性糖毒性组比对照组降低[(97.01±2.05)ng/m L vs(65.12±0.42)ng/m L,(121.40±0.58)ng/m L vs(62.7±0.48)ng/m L],下降49%和94%(P0.05)。HE染色显示急性糖毒性胰岛边界不规则、内部细胞排列不整;透射电镜可见细胞内胰岛素分泌颗粒空泡,线粒体嵴断裂。结论急性葡萄糖毒性使胰岛β细胞内胰岛素储备减少,导致第一时相分泌胰岛素峰值降低及延迟。
[Abstract]:Objective to observe the effect of acute hyperglycemia on the function and morphology of the first phase insulin secretion in mice. Methods C57/BL 6J mice were infused with 20% high glucose solution for 4 h after jugular vein intubation to establish acute glucose toxicity mice model. Intraperitoneal glucose tolerance test (intraperitoneal glucose tolerance test,IPGTT) and oral glucose tolerance test (oral glucose tolerance test,OGTT) were used to evaluate glucose tolerance and insulin secretion function. HE staining and electron microscope were used to observe the changes of islet morphology and subcellular structure of insulin secretory granules. Results compared with the control group, the blood glucose level of 15 min in the IPGTT group was significantly increased [(10.3 卤0.33) mmol/L vs (19.3 卤1.66) mmol/L], and increased by 87% (P0.05 卤0.31) compared with the control group [(9.8 卤0.31) mmol/L vs (18.16 卤1.01) mmol/L] and 85% (P0.05). In the acute glucose toxicity group, the basal state (glucose concentration 2. 8 mmol/L) and high glucose concentration (16. 7 mmol/L) were stimulated. Insulin secretion decreased significantly [(0.481 卤0.003) ng/m L vs (0.702 卤0.121 ng/m L, (2.43 卤0.03) ng/m L vs (4.07 卤0.34 ng/m L], and decreased by 46% and 67%, respectively (P0.05). Compared with the control group, the acute glucose toxicity group decreased [(97.01 卤2.05) ng/m L vs (65.12 卤0.42 ng/m L, (121.40 卤0.58) ng/m L vs (62.7 卤0.48 ng/m L], decreased by 49% and 94% (P0.05). HE staining showed irregular boundary of acute glycosylated islets and irregular arrangement of inner cells. Conclusion Acute glucose toxicity can decrease the insulin reserve in islet 尾 cells and lead to the decrease and delay of insulin secretion in the first phase.
【作者单位】：首都医科大学附属北京安贞医院内分泌代谢科;
【基金】：国家自然科学基金资助项目(81641027) 教育部留学回国基金资助项目(2012-940) 北京市科委科研基金资助项目(Z131100004013044) 北京市学科带头人基金资助项目(2013-2-006)
【分类号】：R587.1

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