D-松醇复配Mn2+对2型糖尿病大鼠的降血糖作用及其机制的研究

目的:研究D-松醇复配Mn2+对2型糖尿病大鼠的降血糖作用并探讨其作用机制。方法:选用SPF级雄性大鼠进行实验,高糖高脂饲料喂养配合注射链脲佐菌素(STZ)诱导建立2型糖尿病(T2DM)模型。实验动物分为空白对照组、模型对照组、阳性对照组、D-松醇组和低、中、高复配Mn2+组,灌胃期间每周定时测体重和空腹血糖(FBG),4周后测定口服葡萄糖耐量(OGTT)和胰岛素耐量(ITT),5周后处死并对其糖化血清蛋白(GSP)、空腹血清胰岛素(FINS)等生理生化指标进行测定,计算胰岛素敏感性指数(ISI)和胰岛β细胞功能指数(HOMA-β)。并采用实时荧光全定量分析(RT-PCR)实验检测AMPK信号通路相关基因mRNA表达水平。结果:与模型对照组相比,剂量组均可显著性降低T2DM大鼠空腹血糖值(p<0.05),高剂量复配组血糖值极显著降低(p<0.01)。此外,与D-松醇组相比,高剂量复配组的FINS和GSP极显著降低(p<0.01)。与模型对照组相比,ISI-1、ISI-2和AMPKα-2基因mRNA表达水平显著上调(p<0.05),且高剂量组与D-松醇组相比极显著性上调(p<0.01)。高剂量复配组AMPKα-1和GLUT4基因mRNA表达水平显著上调(p<0.05),PGC-1α、PEPCK和G6Pase基因mRNA表达水平显著下调(p<0.05)。结论:D-松醇复配Mn2+提高了T2DM大鼠对葡萄糖的耐受能力,缓解胰岛素抵抗症状,提高机体对胰岛素的敏感性,其作用机制可能涉及AMPK参与的抑制糖异生等生化调控过程起到降血糖作用。

Hypoglycemic Effects and Mechanism of D-pinitol Compound with Mn2+on Type 2 Diabetes Mellitus Rats

Objective:The objective of this work was to explore the hypoglycemic effects of D-pinitol compound with Mn2+ on type 2 diabetes mellitus rats and underling mechanism. Methods:A model of type 2 diabetes mellitus(T2DM)was established by feeding high-fat diet and streptozocin(STZ)injecting to male rats. The rats were divided into the normal group,control group,positive control group,D-pinitol group,low,medium and high complex Mn2+ group.Body weight and fasting blood glucose(FBG)were tested each week. Oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)was tested after four-week-treatment. The contents of glycated serum protein(GSP)and fasting insulin(FINS)were determined after five-week-treatment and insulin sensitivity index(ISI)and pancreatic β cell function index(HOMA-β)were calculated. The expression of AMPK genes was detected with real-time polymerase chain reaction(real-time PCR). Results:Compared with the model group,the hypoglycemic effects of dosage groups increased significantly(p<0.05),and the high combined group increased significantly(p<0.01).Compared with the D-pinitol group,the FINS and GSP of the high combined group increased significantly. Compared with the model group,the mRNA expression levels of ISI-1,ISI-2 and AMPKα-2 increased significantly(p<0.05),and the high combined group increased significantly(p<0.01).The mRNA expression levels of AMPKα-1 and GLUT4 increased significantly(p<0.05)while PGC-1α,PEPCK and G6pase mRNA expression decreased significantly(p<0.05)in the high combined group. Conclusion:D-pinitol compound with Mn2+ could improve the body’s sensitivity to insulin,moreover,it has a positive effect on hypoglycemic activity through AMPK signaling pathway.