目的 探讨栀子苷对糖尿病小鼠的降糖作用及机制。方法 C57BL/6J小鼠通过一次性注射90 mg/kg链脲佐菌素（STZ）后结合4周喂养高脂食料建立糖尿病小鼠模型。实验小鼠随机分为对照组、模型组、栀子苷（100 mg/kg）治疗组。ig给药，每日1次，定期检测小鼠空腹血糖及体质量。治疗30 d后，检测小鼠空腹血浆胰岛素和口服糖耐量（OGTT）变化。采用胰岛素及Ki67抗体对小鼠胰腺组织切片进行免疫荧光染色，观察胰腺组织形态学的改变，以及胰岛β细胞增殖情况；Western Blotting方法检测小鼠肝脏组织中p-Akt、p-GSK-3β蛋白表达水平。结果 与模型组相比，栀子苷治疗组小鼠血糖水平降低，体质量下降，而血浆胰岛素水平升高，OGTT有所改善；胰腺组织切片免疫荧光染色结果表明，模型组小鼠胰岛结构被破坏，而栀子苷治疗组有明显改善，并且观察到Ki67表达，表明栀子苷能够促进胰岛β细胞增殖；栀子苷治疗组小鼠肝脏中Akt、GSK-3β蛋白磷酸化水平较模型组均有显著上调。结论 栀子苷能够有效改善糖尿病模型小鼠的高血糖症状，并增加血浆胰岛素水平，其作用可能与促进胰岛β细胞增殖，激活胰岛素受体下游Akt通路有关。

Objective To investigate the hypoglycemic effect of geniposide and to explore the mechanism. Methods The diabetic mice were induced by a single dose of 90 mg/kg streptozotocin (STZ) injection followed by four-week high-fat diets and randomly divided into three groups: normal control (con), diabetic model (diab), and geniposide (gen, 100 mg/kg) groups. Body weight and fasting blood glucose were measured during the treatment. Thirty days later, the oral glucose tolerance test (OGTT) was performed, blood samples were collected to measure insulin concentration in plasma. The morphological changes of pancreas pathology and β-cell proliferation were examined by immuno-fluorescent staining of insulin and Ki67. The phosphorylations of AKT and GSK-3β (p-AKT and p-GSK-3β) in liver tissues were detected by Western blotting assay. Results Compared with the diab group, geniposide showed significantly hypoglycemic effect, together with lowering body weight, increasing the insulin content in plasma, and improving OGTT. The immuno-fluorescent staining showed the islets destruction caused by hyperglycemia was recovered by geniposide. The β-cell proliferation presented by Ki67 staining increased as compared with that in the diab group. Moreover, both p-Akt and p-GSK-3β levels in the liver tissue were upregulated by geniposide remarkably. Conclusion The present study demonstrates that geniposide could ameliorate the hyperglycemia in diabetic mice by enhancing the pancreatic β-cell proliferation and activation of AKT signaling pathway in liver.

国家自然科学基金资助项目（81102488）；江苏省自然科学基金资助项目（BK2011865）