RESUMO
Aim To observe the effect of agiophyllum oligo saccharides ( AOS) on reducing blood sugar, im-proving insulin resistance on diadetic Goto-Kakizaki ( GK) rats, and to explore the possible mechanism. Methods The type 2 diabetes GK rats were divided into six groups: model control group ( MC ) , Glenn benzene urea group ( GLB ) , high agriophyllum squar-rosum coarse oligosaccharides ( AOS-H ) , medium ( AOS-M ) , low dose group ( AOS-L ) , homologous Wistar rats as normal control ( NC ) . All animals were administered with AOS by oral gavage, for 8 weeks. The fasting blood glucose ( FBG) , random blood sugar ( RBG) , glucose tolerance ( OGTT) were tested before and after administration. No fasting sugar load status before and after dosing changes in blood glucose and serum insulin level in rats were measured in the previ-ous 8 weeks. At the end of administration, the fasting serum glucose ( FPG) , insulin ( FINS) , OGTT and in-sulin resistance index ( HOMA IR) in fasting rats were analyzed. Lastly, the pathological changing of pancreas was observed by HE staining. Results The blood glucose of fasting GK rats was not influenced after using AOS. However, the random blood glucose significantly reduced, the glucose tolerance was improved and AUC was obviously reduced (P < 0. 01) after using AOS. The best effect was on AOS-M group, which was similar with Glenn benzene urea. Through our research, we found AOS could promote release of insulin. This best effect was on AOS-M and AOS-L groups, and the time and quantity of release were better than Glenn benzene urea. Finally, AOS inhibited the pathological changes of islet tissue on GK rats, increased the quantity of pancreas and islet cells. Compared with model group, the changing of islet structure was significantly reduced in AOS group. Conclusion AOS could obviously improve insulin resistance and lower blood sugar, and the mechanism of this effect may be related with rapidly promoting insulin release, increasing the islet cell proliferation,and improving the function of islet.
RESUMO
Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.