Anti-diabetic Mechanism Of AOE Through Regulating MiRNA Expression Down-regulates PTEN

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AOE regulates Expression profile of micro RNA in the liver on 57BL/Ks J db-/db-miceObjective Micro RNAs?miRNAs?involvement in the pathology of obesity and type2 diabetes has received limited research attention to date.Emerging evidence suggests that Alpinia oxyphylla may exhibit antioxidant and anti-diabetic activities.To determine the micro RNA expression profiles in the livers of db-/db-mice treated with Alpinia oxyphylla extract?AOE?.Methods 24 mice were divided into three groups: 8 DB/DB mice and 16 db-/dbmice,DB/DB mice group and db-/db-H₂0 mice group were given placebo?physiological The saline?,db-/db-AOE group was administered 500 mg/kg AOE once daily via the intragastric route for 8 weeks.The euthanized mice were dissected and miRNAs were extracted from the liver and sequenced using standard methods.The target genes were predicted using a clustering method and confirmed by qRT-PCR.Results Sequencing showed that in the DB/DB mice liver,there were 19 miRNA expression differences in the db-/db-H₂0 group of mice,of which 8 were down-regulated and 11 were up-regulated;in db-/db There were 7 differentially expressed miRNAs in the AOE mice liver,of which 5 were down-regulated and 2were up-regulated.In both groups,mmu-mi R-423-5p and mmu-mi R-598-3p were identified.The expression of mmu-mi R-598-3p and mmu-mi R-423-5p in the liver of db-/db-AOE mice was higher than that of DB/DB and db-/db-without AOE treatment.H₂0 group.Conclusions Compared with the db-/db-H₂0 mice,we identified 19 miRNA expression differences in the DB/DB group and 7 miRNA expression differences in the db-/db-AOE group.Most of the miRNAs found in this study were previously associated with obesity or diabetes,and it was confirmed that the expression of the two miRNAs?mi R-598 and mi R-423?was suppressed in db-/db-H₂0 mice but was treated by AOE.Its expression may be restored.These two miRNAs may be involved in important signaling pathways,including MAPK and Ras signaling pathways.Part ? Anti-diabetic Mechanism of AOE Through Regulating PTEN ExpressionObjectives Diabetes is characterized by high blood glucose levels.Increased levels of reactive oxygen species?ROS?may disrupt insulin signaling and lead to insulin resistance.AOE has a powerful antioxidant activity and therefore can inhibit the development of insulin resistance.The purpose of this study was to investigate the effect of AOE on blood glucose,insulin,and lipid levels in db-/db-mice in animal models of type 2 diabetes.AOEs at 100,300,and 500 mg/kg were measured by measuring changes in body weight and blood glucose concentrations in mice.The effects of db-/db-mice on the glucose tolerance,plasma insulin concentration,plasma lipid profile,liver lipid profile and urinary protein were measured at 500 mg/kg AOE.Methods AOE was administered to these mice at different doses?100,300,and 500mg/kg?for 8 weeks.The free radical scavenging activity of AOE was measured with2,2-diphenyl-1-picrylhydrazyl?DPPH?and the concentration of AOE was measured.The treated mice were changed in body weight and plasma glucose concentration.The mice were treated with AOE 500 mg/kg for 8 weeks and their OGTT,plasma insulin levels,plasma lipid levels,and renal function were determined.After 8 weeks,the mice were sacrificed.The kidney and liver tissues were dissected and the protein expression levels of PTEN in kidney and liver tissues were detected by Western Blot.Results The 10g/L AOE showed the best antioxidant capacity to eliminate DPPH free radicals.In DB/DB and db-/db-mice and after 8 weeks of treatment with different concentrations of AOE,there was no significant difference in body weight between any groups.Compared with the db-/db-H₂0 group,plasma glucose levels were significantly decreased in the AOE-treated groups,and the highest dose of AOE500 mg/kg was the most effective in reducing blood glucose levels.Glucose stimulation significantly increased blood glucose concentrations in mice in the db-/db-H₂0 group,whereas AOE500 mice showed significantly suppressed blood glucose concentrations at 30,60 and 90 minutes after glucose load.The effect of AOE on plasma insulin concentration was significantly higher plasma insulin concentrations in the db-/db-H₂0 group than in the DB/DB group and the db-/dbAOE group.Plasma concentrations of triglyceride and cholesterol in the db-/dbgroup were 15.0% and 10% lower than those in the db-/db-mice,respectively?P <0.05?.Compared with DB/DB mice,urinary albumin?P <0.05?,creatinine?P <0.05?,and BUN?P <0.05?were significantly increased in db-/db-H₂0 mice.In the db-/db-AOE group,24-hour urinary albumin excretion was 0.62±0.17 mg,which was significantly lower than that in the db-/db-H₂0 group?1.27±0.31 mg,P < 0.05?,but it was still higher than DB/DB group?0.32±0.04 mg,P<0.05?.The concentration of creatinine and BUN also decreased significantly after AOE treatment?P < 0.05?.In the db-/db-H₂0 mice,the expression of PTEN protein in the liver and kidneys was enhanced,but after treatment with AOE500 in db-/db-mice,the expression of PTEN protein was significantly decreased?P < 0.05?.Conclusion AOE can increase plasma insulin levels,improve renal function,and reduce PTEN expression in T2 DM mice by lowering blood glucose and oxidative stress,ultimately improving hyperglycemia and hyperlipidemia.Therefore,AOE may be used as a new type of drug or functional dietary supplement to prevent diabetes.