二甲双胍对妊娠期糖尿病小鼠模型糖代谢 及胰岛功能的远期作用

Long-term effect of metformin on the glucose metabolism and islet function in mice with gestational diabetes mellitus

摘要:

目的：探讨妊娠期糖尿病（gestational diabetes mellitus，GDM）小鼠模型老年期糖代谢特点及孕期二甲双胍治疗对GDM小鼠胰岛素抵抗和胰岛功能的远期影响。方法：将小鼠随机分成对照组（n=6）、GDM组（n=6）、治疗组（n=6），采用高脂饮食诱导建立GDM动物模型，治疗组于孕11.5~17.5 d给予二甲双胍治疗。分娩后均转维持饲料，并定期监测其体质量变化。并于分娩9个月后，应用口服葡萄糖耐量试验（oral glucose tolerance test，OGTT）及胰岛素耐量试验（insulin tolerance test，ITT）检测糖代谢。利用HE染色法观察胰岛的病理学改变。通过免疫组化染色法检测Ki67蛋白在胰腺组织中的表达。结果：分娩2个月后，与对照组相比，GDM及治疗组小鼠体质量增长明显（F=3.875，P=0.044）。与对照组相比，GDM组腹腔注射胰岛素后血糖下降缓慢（P=0.004）。GDM组胰岛萎缩，数目减少。Ki67在对照组胰岛中呈强阳性表达（P=0.032）。结论：GDM小鼠模型分娩后，葡萄糖的调节能力可以基本恢复正常，但是胰岛素抵抗持续存在。进入老年后，胰岛组织萎缩，功能逐渐减退，增殖能力降低。而孕期给予二甲双胍治疗可以增强其老年期的胰岛素敏感性，改善胰岛的病理学改变，但不能改变胰岛组织的增殖能力。

Abstract:

Objective：To investigate the characteristics of glucose metabolism and the effect of metformin treatment on the insulin re－sistance and islet function in elderly mice with the history of gestational diabetes mellitus（GDM）. Methods：The mice were randomly divided into the control group（n=6），GDM group（n=6） and treatment group（n=6）. The animal model was established by high fat diet and the treatment group was administered metformin in the 11.5-17.5d of pregnancy. The body weight was monitored every month after delivery. Nine months after delivery，oral glucose tolerance test（OGTT） and insulin tolerance test（ITT） were adopted to detect the glucose metabolism in elderly mice with GDM history. The pathological changes of islets were observed under HE staining，and the expression of Ki67 in pancreatic tissues was detected by immunohistochemical staining. Results：Two months after delivery，the body weights of GDM and treatment group increased significantly（F=3.875，P=0.044） compared with the control. In GDM group，Glucose decreased slowly after intraperitoneal injection of insulin（P=0.004），islet shrank and the number of islets decreased. The expression of Ki67 was strongly positive in the islets of the control group（P=0.032）. Conclusion：For mice with GDM，blood glucose can return to be normal after delivery，but insulin resistance persists. For the elderly mice with GDM history，the islets present atrophy，function de－generates gradually，and the proliferation ability decreases. Metformin treatment during pregnancy can reverse the elderly insulin re－sistance and improve the pathological changes of islets，but can not change the proliferation ability.