生物钟节律紊乱影响糖尿病小鼠糖代谢及胰岛素分泌的实验研究

目的 探究生物钟节律紊乱对糖尿病肥胖小鼠（ob/ob）糖代谢及胰岛素分泌的影响。方法 选取同体重的6~8周龄C57BL/6及ob/ob小鼠各12只，随机分为对照组（C57组）、糖尿病组（OB组）、对照组+生物钟节律干扰组（C57+CSD组）、糖尿病组+生物钟节律干扰组（OB+CSD组），每组6只。C57+CSD组和OB+CSD组小鼠分别置于高台水环境下干扰其生物钟节律。C57组和OB组小鼠分别置于标准饲养笼中，其生物钟节律不受干扰，动物体重每天监测1次。4周后行小鼠体内腹腔注射葡萄糖耐量实验（IPGTT，2 g/kg），分离实验小鼠胰岛行体外葡萄糖刺激胰岛素分泌实验（GSIS）。结果 C57、C57+CSD和OB组体重分别增长22.92%、0.42%和26.16%，而OB+CSD组下降0.17%。空腹血糖测定显示:OB组与OB+CSD组血糖值水平高于C57组和C57+CSD组（P＜0.05）；IPGTT实验显示:OB组小鼠血糖峰值明显后移，且在15、30、60、90 min的血糖均高于C57组（P＜0.05）；C57+CSD组小鼠各时间点血糖均高于C57组（P＜0.05），OB+CSD组小鼠于120 min的血糖高于OB组（P＜0.05）；体内、体外胰岛素测定显示:C57胰岛素分泌低于OB组（P＜0.05），C57+CSD组胰岛素分泌低于C57组（P＜0.05），OB+CSD组血清及体外胰岛胰岛素分泌低于OB组（P＜0.05）。结论 生物钟节律是维护糖代谢稳态的重要环节，其紊乱可能导致正常及糖尿病小鼠胰岛素分泌的减低。

Experimental Study on the Effects of Biological Clock Rhythm Disorder on Glucose Metabolism and Insulin Secretion in Diabetic Mellitus Mice

Objective To investigate the effects of biological clock rhythm disorder on glucose metabolism and insulin secretion in diabetic mellitus obese mice (ob/ob). Methods 12 C57BL/6 and ob/ob mice, aged 6-8 weeks, were randomly divided into control group (C57 group), diabetic mellitus group (OB group), control group + biological clock rhythm interference group (C57+). CSD group), diabetes mellitus group + biological clock rhythm interference group (OB+CSD group), 6 in each group. The C57+CSD group and the OB+CSD group were each placed in a high-level water environment to interfere with their biological clock rhythm. C57 and OB mice were placed in standard cages, respectively, and their clock rhythms were undisturbed. Animal weight was monitored once a day. After 4 weeks, the mice were intraperitoneally injected with glucose tolerance test (IPGTT, 2g/kg), and the islet glucose-stimulated insulin secretion test (GSIS) was isolated from the mice. Results The body weight of C57, C57+CSD and OB groups increased by 22.92%, 0.42% and 26.16%, respectively, while the OB+CSD group decreased by 0.17%. Fasting blood glucose measurement showed that the blood glucose level of OB group and OB+CSD group was higher than that of C57 group or C57+CSD group (P＜0.05). The IPGTT experiment showed that the blood glucose peak of OB group was significantly shifted back,the blood glucose at 15, 30, 60, 90 min was higher than that in C57 group (P＜0.05). The blood glucose in C57+CSD group was higher than that in C57 group (P＜0.05). OB+CSD mice The blood glucose at 120 min was higher than that in OB group (P＜0.05). In vivo and in vitro insulin assay showed that C57 insulin secretion was lower than that of OB group (P＜0.05), and insulin secretion in C57+CSD group was lower than that of C57 group (P＜0.05). The serum and in vitro insulin secretion of OB+CSD group was lower than that of OB group (P＜0.05). Conclusion The biological clock rhythm is an important link to maintain the homeostasis of glucose metabolism, and its disorder may lead to a decrease in insulin secretion in normal and diabetic mellitus mice.