Cornus Officinalis Affects Glucose And Lipid Metabolism And Skeletal Muscle PI-3K/AKT Signaling Pathway In T2DM Mice

Cornus officinalis refers to the dried,ripe,and stoneless fruit of Cornus officinalisSieb.et Zucc.,which is a member of the Cornaceae plant family.This fruit has been widely prescribed to treat hepatorenal syndrome in China for centuries,and it is also considered as one of the most frequently applied vegetable drugs in the treatment of diabetes mellitus and its complications.Many modern clinical and experimental stuides have reported Cornus officinalis possesses anti-microbico,regulation of the immune,anti-hyperlipidemia and anti-hypoglycemic bioactivities.In this study,we are no longer at the basis research of Cornus officinalis in prevention against diabetes,but at the effect and mechanism of different extractions from Cornus officinalis on insulin resistance and glucose uptake in T2DM mice,which may provide reliable experimental basis for application of Cornus officinalis to treat T2DM.In the present study,the type 2 diabetic mellitus(T2DM)in mice were induced through low-dose(30 mg/kg)STZ and high-fat diet,and the T2DM mice were orally administrated with nano-Cornus officinalis(NC)and alcohol extraction of Cornus officinalis(EC)at different doses for 4 weeks.For mechanistic studies,the biochemical index,the key genes expression about PI-3K/AKT signal pathway in skeletal muscle and pancreatic tissues were measured using kits,western blotting,reverse transcription polymerase chain reaction and H&E staining,respectively.The main conclusions can be drawn as follows:(1)The results of this study indicated that NCHG,NCMG,NCLG,ECHG,ECMG,ECLG and PCG diabetic mice significant decreases of FBG,PBG,AUC,the serum lipid parameters(TC,TG,LDL-C),FINS,HOMA-IRI,while the serum HDL-C,HOMA-ISI and HOMA-p were restored much closer to those of normal rats.(2)The inflammation and oxidative stress in liver were being test,and the results indicated that NC and EC lowered the release of hepatic inflammatory factors(CRP,TNF-α,IL-6)and MDA levels and the adverse effect on hepatic T-SOD activities.(3)Also NC and EC showed great inhibitory activity by decreasing GLUT-4 mRNA,INSR mRNA,PI-3K mRNA,AKT mRNA,GLUT-4,p-INSR,p-PI-3K and p-AKT expression in skeletal muscle of T2DM mice.Furthermore,NC and EC obviously alleviated the histopathologic changes including liver and pancreas fatty degeneration and necrosis.(4)In addition,we found that EC was more active of anti-diabetic than NC.These findings demonstrate that the antidiabetic potential of NC and EC are mainly through their modulatory effects on β-cell dysfunction,insulin resistance,pathoglycemia and dyslipidemia by increasing expression and promoting translocation of GLUT-4 and PI-3K/AKT pathway.The results also suggest that NC and EC achieves protective effect on liver and pancreas damage in T2DM mice.In addition,we found that EC was more active of anti-diabetic than NC.