HOU Dan, LIU Tong-hua. Effect and Mechanism of Oleuropein on Glucose Metabolism of Liver in Diabetic Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(23): 134-139.
DOI:
HOU Dan, LIU Tong-hua. Effect and Mechanism of Oleuropein on Glucose Metabolism of Liver in Diabetic Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(23): 134-139. DOI: 10.13422/j.cnki.syfjx.20182025.
Effect and Mechanism of Oleuropein on Glucose Metabolism of Liver in Diabetic Mice
摘要
目的:通过观察橄榄苦苷(OL)对糖尿病小鼠肝脏糖代谢的作用并探讨其机制。方法:自发性糖尿病小鼠db/db小鼠40只,随机分为模型组,二甲双胍组(0.13 g·kg-1),橄榄苦苷高、低剂量组(0.05,0.025 g·kg-1),每组10只,另设同周龄C57BL/6J小鼠10只为正常组。治疗6周后,观察各组小鼠的空腹血糖(FBG),胰岛素(Fins)水平,计算胰岛素抵抗指数(HOMA-IR),口服葡萄糖耐量实验(oral glucose tolerance test,OGTT)以及体质量,血肌酐(SCr),尿素氮(BUN),天门冬氨酸氨基转移酶(AST),肝糖原含量;采用实时荧光定量PCR(Real-time PCR)检测葡萄糖-6-磷酸酶(glucose-6-phosphatase,G-6-P),磷酸化-烯醇式丙酮酸(phosphoenolpyruvate carboxykinase,p-EPCK)mRNA表达;蛋白免疫印迹法(Western blot)检测叉头转录因子1(forehead box-containing protein of the O subfamily 1,FoxO1),蛋白激酶B(protein kinase B,Akt)蛋白表达。结果:与模型组比较,OL组体质量,FBG,Fins,HOMA-IR显著降低(P<0.01);肝糖原含量明显升高(P<0.05,P<0.01);OGTT实验120 min血糖显著降低(P<0.01);小鼠肝脏p-EPCK,G-6-P mRNA表达显著降低(P<0.01),Akt,FoxO1磷酸化水平明显升高(P<0.05,P<0.01)。结论: OL具有抑制糖异生发挥降糖、改善胰岛素抵抗作用,机制可能与其升高Akt-FoxO1磷酸化,减少p-EPCK,G-6-P转录有关。
Abstract
Objective:To explore the effect and mechanism of olivine (OL) on glucose metabolism of liver in diabetic mice. Method:Totally 40 db/db mice of spontaneous diabetes were randomly divided into model group
metformin group (0.13 g·kg-1)
and high and low-dose olivine group (0.05
0.025 g·kg-1)
with 10 mice in each group
and 10 C57BL/6J mice were set as normal group. After 6 weeks of treatment
fasting blood glucose(FBG)
Fins
HOMA insulin resistance index(HOMA-IR)
oral glucose tolerance test (OGTT)
body weight
serum creatinine (SCr)
blood urea nitrogen(BUN)
aspartate aminotransferase(AST) and liver glycogen content were measured. Real-time PCR was used to detect the mRNA expressions of glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate carboxykinase (p-EPCK). Western blot was used to detect the protein expressions of forehead box-containing protein of the O subfamily 1 (FoxO1) and protein kinase B (Akt). Result:Compared with model group
body weight
FBG
Fins and HOMA-IR in OL group decreased significantly (P<0.01); liver glycogen content increased significantly in OL group (P<0.05
P<0.01); blood glucose significantly decreased at 120 min of OGTT test (P<0.01); the mRNA expressions of p-EPCK
G-6-P in mouse liver decreased significantly (P<0.01)
and the phosphorylation levels of Akt
FoxO1 increased significantly (P<0.05
P<0.01). Conclusion:OL can inhibit gluconeogenesis
decrease FBG
and alliviate insulin resistance
which may be related to the increase of phosphorylation of Akt-FoxO1 and the decrease of transcription of p-EPCK and G-6-P.