Objective To clarify the impairment mechanisms of acute hyperglycemia in the first-phase insulin se-cretion in mice. Methods The mouse model of acute glucose toxicity was established by glucose infusion through jugular vein catheterization. The glucose and insulin levels were assessed by IPGTT and OGTT in the mice of acute hyperglycemia and control groups. The histology of pancreatic islets was observed using HE staining and the insulin granules and other cy-toplasmic organelles were observed by electron microscopy. Results The mouse model of acute hyperglycemia was suc-cessfully established. The IPGTT showed that the blood glucose level was decreased by 87% ( 10. 3 ± 0. 33 mmol/L vs. 19. 3 ± 1. 66 mmol/L) at 15 min in the acute hyperglycemia group compared with the control group. The OGTT showed that the blood glucose level was decreased by 85% (9. 8 ± 0. 31 mmol/L vs. 18. 16 ± 1. 01 mmol/L) at 30 min in the acute hy-perglycemia group compared with the control group. However, the peak values of insulin secretion were delayed in both IPGTT and OGTT. Insulin levels at 2. 8 and 16. 7 mmol/L glucose stimulation in the acute hyperglycemia group was de-clined by 46% and 67% than the control group, respectively (P<0. 05). Residual insulin content in isletβcells was de-clined by 49% at 2. 8 mmol/L and 94% at 16. 7 mmol/L glucose infusion than the control group (P<0. 05). The histolo-gy showed irregular structure of pancreatic islets in the acute hyperglycemia group. The electron microscopy revealed that the amount of insulin granules was decreased, and more cytoplasmic vacuoles and swollen mitochondria were observed. Conclusions Acute intravenous glucose load decreases insulin content of isletβcells, leading to decrease and delay of the first-phase insulin secretion.%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(intraper-itoneal 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%(P<0.05),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%(P<0.05),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/mL vs(0.702±0.121)ng/mL,(2.43±0.03)ng/mL vs(4.07±0.34)ng/mL],分别下降46%和67%(P<0.05);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/mL vs(65.12±0.42)ng/mL,(121.40±0.58)ng/mL vs(62.7±0.48)ng/mL],下降49%和94%(P<0.05).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.
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