Tan Hui-Wen, Zhao Nai-Qian, Yu Ye-Rong, Han Li-Na, Zhang Xiang-Xun
Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 Jan;48(1):71-75.
To analysis the effects of glucoxicity and lipotoxicity on the function and apoptosis of pancreatic β-cells.
The levels of circulating glucose and free fat acids (FFAs) were elevated by infusion dextrose and fat emulsion in high-fat obese rats. The insulin resistance model obese rats were divided into four gourp: obese group with saline infusion (OB-NS group, =7), obese group with glucose infusion (OB-GS group, =9), obese group with Lipid emulsion infusion (OB-FFA group, =8), obese group with glucose and lipid emulsion infusion (OB-FG group, =9). Five rats fed with general diet were taken as normal group (NC group).Plasma FFAs and β-hydroxybutyric acid (β-HBA) concentrations were determined by an enzymatic colorimetric method. An intravenous glucose tolerance test (IVGTT) was performed to examine the glucose-stimulated insulin secretion and immunohistochemical staining to detect the storage volume of insulin. FFA and β-HBA concentrations were measured at baseline and post-infusion. The apoptosis of pancreatic β-cell was detected by end labeling technique (TUNEL).
Glucose infusion rate (GIR) of obese rats was significantly lower than that in NC group [(10.82±1.8) mg/(kg·min) vs. (25.21±1.7) mg/(kg·min), <0.05], confirming insulin resistance rat model successfully established. The insulin secretion peak load time of OB-FG group rats delayed, and the serum insulin level was significantly lower than that of NC group and OB-NS group during IVGTT. The differences were statistically significant ( <0.05). Compared with OB-NS and NC groups, storage volume of insulin of OB-GS group reduced, and β cell apoptosis rate elevated significantly.
Glucolipotoxicity could induce ketone overproduction, insulin resistance and defective insulin secretion.
分析糖毒性和脂毒性对胰腺β细胞功能及凋亡的影响。
通过向高脂肥胖大鼠输注葡萄糖和脂肪乳剂来升高循环葡萄糖和游离脂肪酸（FFA）水平。将胰岛素抵抗模型肥胖大鼠分为四组：输注生理盐水的肥胖组（OB-NS组，n = 7）、输注葡萄糖的肥胖组（OB-GS组，n = 9）、输注脂肪乳剂的肥胖组（OB-FFA组，n = 8）、输注葡萄糖和脂肪乳剂的肥胖组（OB-FG组，n = 9）。选取5只喂食普通饮食的大鼠作为正常组（NC组）。采用酶比色法测定血浆FFA和β-羟基丁酸（β-HBA）浓度。进行静脉葡萄糖耐量试验（IVGTT）以检测葡萄糖刺激的胰岛素分泌，并通过免疫组织化学染色检测胰岛素的储存量。在基线和输注后测量FFA和β-HBA浓度。采用末端标记技术（TUNEL）检测胰腺β细胞的凋亡。
肥胖大鼠的葡萄糖输注率（GIR）显著低于NC组[（10.82±1.8）mg/（kg·min）对（25.21±1.7）mg/（kg·min），P<0.05]，证实成功建立胰岛素抵抗大鼠模型。OB-FG组大鼠的胰岛素分泌峰值负荷时间延迟，且在IVGTT期间血清胰岛素水平显著低于NC组和OB-NS组。差异具有统计学意义（P<0.05）。与OB-NS组和NC组相比，OB-GS组的胰岛素储存量减少，β细胞凋亡率显著升高。
糖脂毒性可诱导酮体过度产生、胰岛素抵抗和胰岛素分泌缺陷。
