动物造模,急性高血糖 z-bio 2022-06-06 305

　　Objective: To observe the function and morphological changes of acute hyperglycemia affecting 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 a mouse model of acute glucotoxicity. Intraperitoneal glucose tolerance test (IPGTT) and oral glucose tolerance test were performed. Oral glucose tolerance test (OGTT) was used to evaluate glucose tolerance and insulin secretion. HE staining and electron microscopy were used to observe the morphological changes of islets and the subcellular structure of insulin secreting granules in cells.

　　Results: In the IPGTT experiment, the 15-min blood glucose level in the acute glucotoxicity group was significantly higher than that in the control group [(10.3±0.33) mmol/L vs (19.3±1.66) mmol/L], an increase of 87% (P<0.05). The blood glucose level at 30 min increased significantly compared with the control group [(9.8±0.31) mmol/L vs (18.16±1.01) mmol/L], an increase of 85% (P<0.05), and the early peak of insulin secretion was impaired and the secretion was delayed. In the GSIS experiment, the insulin secretion of the acute glucotoxicity group was significantly lower than that of the control group at the basal state (glucose concentration 2.8 mmol/L) and after stimulation with high glucose (16.7 mmol/L) [(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], decreased by 46% and 67% respectively (P<0.05); the results of insulin content determination showed that the acute glucotoxicity group was more Control group decreased [(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], decreased by 49% and 94% (P< 0.05). HE staining showed that acute glucotoxic islet borders were irregular and internal cells were irregularly arranged; transmission electron microscopy showed intracellular insulin secretion granule vacuoles and mitochondrial cristae rupture.

　　CONCLUSION: Acute glucotoxicity reduces the insulin reserve in islet β cells, resulting in a decrease and delay in the peak insulin secretion in the first phase.