Protective Effects Of Naringenin On Type 2 Diabetes Mellitus And Its Molecular Mechanisms

Objective: Diabetes Mellitus(DM)is a kind of severe disease affectting human health,of which 90%-95% is type 2 DM(T2DM).The effective prevention of T2 DM,a global focus point nowadays,is also an important problem that China needs to solve urgently.Naringenin is one of the most abundant hydroflavonoids,recent studies have demonstrated that it has a preventive and therapeutic effects on T2 DM.There studies find naringenin can reduce fasting blood glucose and glycosylates hemoglobin levels in T2 DM rats.However,the mechanisms and specific molecular targets of naringenin in the prevention and treatment of T2 DM are still unclear.The inhibitory effect of naringenin on insulin resistance of T2 DM is controversial and needs to further research.Method: MIN6 cells,HepG2,and 3T3-L1 cells were cultured and treated in following ways respectively: firstly,high glucose injury model of MIN6 was established by being cultured in a high-glucose medium,the insulin resistance model of3T3-L1/HepG2 cells were cultured in a high glucose/high insulin medium.Next,miR-375 mimic and inhibitor were transfected into MIN6 model cells,miR-29 b mimic and inhibitor were transfected into HepG2 and 3T3-L1 model cells.Then,the treated three cells were grouped by the intervention of different concentrations of naringenin.MTT was used to detect the proliferation activity of three kinds of cells after naringenin intervention.GOD was used to detect the effect of naringenin on the glucose uptake and insulin sensitivity of HepG2 and 3T3-L1 cells.Furthermore,ELISA was used to determine the insulin release ability of MIN6 cells.QRT-PCR and Western Blotting were used to detect the expression of IRS-1,AKT/p-AKT and GLUT4 gene or protein.Results: 1.Naringenin intervention inhibited the reduced proliferation of MIN6 high glucose model cells and HepG2/3T3-L1 IR model cells,showing a dose-effect relationship.Naringenin intervention reversed the decline of glucose uptake ability and insulin sensitivity in Hep G2/3T3-L1 IR model cells,there was a dose-effect relationship.2.Naringenin intervention inhibited the decrease of the high glucose-induced insulin secretion ability of MIN6 high glucose model cells via mi R-375.3.Naringenin intervention reversed the decreased genes or proteins expression of IRS-1,AKT/p-AKT,and GLUT4 in 3T3-L1 IR model cells.naringenin intervention inhibited the gene and protein expression of IRS-1,AKT/p-AKT in HepG2 IR model cells,but had no effecton the expression of the GLUT4 gene.4.Naringenin intervention reversed the gene and protein expression of IRS-1,AKT/p-AKT and GLUT4 in 3T3-L1 IR model cells via miR-29 b.Naringenin intervention increased the gene and protein expression of IRS-1and AKT/p-AKT in HepG2 IR model via miR-29 b,but had no effect on GLUT4 gene expression.Conclusion: Naringenin increased the proliferation activity,and inhibited the decrease of insulin secretion activity by regulating the high expression of miR-375 in MIN6 cells.Naringenin mediated the expression of IRS/Akt/Glut4 signaling pathway-related proteins by inhibiting the high expression of miR-29 b in HepG2/3T3-L1 cells.These ultimately enhance uptake of glucose on cells,leading to altering the effect of insulin resistance and increasing cellular sensitivity to insulin.This topic researched the role of naringenin in improving T2 DM and its molecular mechanism by selecting multiple targets from multiple aspects,confirming that naringenin can be used as an effective means of prevention and treatment of T2 DM which provides a new idea for effective prevention and treatment of T2 DM.