Abstract: Objective:To investigate the effects of Dendrobium candidum (DC)on the insulin resistance in the MKR mice and the MIN6 cells, and to illuminate the possible mechanisms. Methods:The MKR mice aged 9 weeks were randomly divided into 4 groups,and the mice in various groups were treated with 10,20,40 g·kg^-1 DC and normal saline(blank control group) by gavage,respectively,for 6 weeks.The blood glucose levels of the mice in various groups were detected bi-weekly,and the optimum concentration of DC in reducing the glucose level.The male MKR mice aged 8 weeks were randomly divided into control group,DC group,Met group and Met+DC group.The mice were treated with normal saline and the corresponding drugs for 8 weeks,and the blood glucose levels of the mice were determined.Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed after administration.The qPCR method was used to detect the expression levels of genes related to glucose and lipid metabolism in liver and subcutaneous fat tissues of the mice.The MIN6 cells cultured in vitro were divided into control group,high concentration of palmitic acid(H-PA) group,high concentration of glucose (H-Glu) group,H-PA+H-Glu group,H-PA+DC group,H-Glu+DC group,and H-Glu+H-PA+DC group.MTT method and ELISA method were used to detect the proliferation activities and insulin secretion levels of cells in various groups.Flow cytometry was used to measure the apoptotic rates in various groups.Western blotting method was used to detect the protein expression levels of PI3K/AKT/signaling pathway in the cells in various groups. Results:In vivo,the optimum concentration of DC in reducing the blood glucose level was 20 g·kg^-1·d^-1.Compared with control group,the blood glucose level of the mice in DC,Met and Met+DC groups were decreased significantly (P<0.05);compared with DC group and Met group,the blood glucose level of the mice in Met+DC group was decreased (P<0.05). Compared with DC group and Met group,the glucose tolerance and insulin sensitivity were increased,and the insulin resisitance was improved.Compared with control group,the Pepck mRNA expression level in liver tissue of the mice in Met+DC group was decreased significantly(P<0.05),and the GCK mRNA expression level was increased significantly (P<0.05);the Ppar-γ mRNA expression level in subcutaneons fat tissue of the mice in Met group and Met+DC group were increased significantly(P<0.05).In the MIN6 cells,160 μmol·L^-1and 30 μmol·L^-1 were confirmed to use as the end concentrations of H-PA and H-Glu to induce the insulin resistance,and the cells in various groups were treated with 1.44 g·L^-1 DC.Compared with H-PA group,H-Glu group and H-PA+H-Glu group,the insulin secretion levels of MIN6 cells in H-PA-DC group,H-Glu+DC group and H-PA+H-Glu+DC group were increased significantly(P<0.05),the apoptotic rates were decreased,and the expression levels of p-IRSp-1, p-PI3K and p-AKT proteins was increased significantly(P<0.05);the expression level of p-GSK3β protein in H-PA+H-Glu+DC group was significantly decreased(P<0.05). Conclusion: DC can ameliorate the insulin resistance in the MKR mice. The effect of hypoglycemic therapy is more obvious with metformin in combination. In vitro, DC can improve the palmitic acid and glucose-induced insulin resistance through the PI3K/AKT signaling pathway and increase the insulin secretion level and reduce the apoptotic rates.

Key words: glucose metabolism, Dendrobium candidum, mice, MKR, MIN6 cells, insulin resistence