| Aims:establish a rat model of type 2 diabetes mellitus to determine the effects of Columbinon blood glucose, glut4 in skeletal muscle and the bingding capacity of insulin receptor inliver,astoprobeitshypoglycemicmechanisms.Methods:(1)Sprague-Dawley rats were divided into two groups. groupâ… received a standarddiet; groupâ…¡received a high-fat diet for 3 months and then intraperitoneally injected withstreptozotocin(STZ, 30mg/kg) to establish hyperglycemic rats. The diabetes rats weredivided into four groups: diabetes control, diabetes+low-dose Columbin (25mg/kg),diabetes+high-dose Columbin (50mg/kg), and diabetes+metformin (200mg/kg). Theanimals were treated for 4 weeks. Fasting blood glucose concentration, serum insulin,cholesterol, triglycerides, free fatty acid, weight, insulin sensitivityindex (ISI) and glucosetoleranceweredeterminedtoevaluatehypoglycemiceffects.(2)Allratswerekilledattheendoftheexperiment,apartofliverandskeletalmusclewas isolated to extract liver membrane protein and skeletal muscle membrane protein. Theamount of glut 4 in the sarcolemmal menmbrane compartment, as well as that contained in the intracellular compartment, was determined by Western blotting. The hepatocyticmembranesamples were reactedwithdifferent concentrations of125-I-insulinformeasuringthebingdingcapacityofinsulinreceptor;Results:(1)The HFD-fed rats exhibited significant increase in serum insulin, totalcholesterol(TC), triglycerides (TG) and free fatty acid (FFA) levels(p<0.05) ,showedsignificant reduction in insulin sensitivity index(ISI) as compared to NPD-fed control rats(p<0.05).Except normal group, other groups rats showed reduction in the weight, but have nosignificance as compared to the DM control group(p>0.05). During the experiment, thefasting blood glucose of the DM group rats was stable. The fasting blood glucose reducedin the low-dose columbin group, high-dose columbin group and metformin group, in the14days, thefastingbloodglucosereducedby15.04%,19.65%,20.18%respectively,reducedsignificantly as compared to the DM control group(p<0.05). In the 28days, the fastingblood glucose reduced by 24.97%,30.85%,42.79% respectively, showed significantreduction in the low dose group(p<0.05) and significant remarkably reduction in the highdosegroupandmetformingroup(p<0.01). ComparedwithDM control group,bloodinsulinshowed no significant increase in all groups (p>0.05), ISI in the DM control group waslower remarkably than the normal group (p<0.01), and ISI in all groups were higher thantheDM control group(p<0.05).Effect ofcolumbinonglucosetolerancetest indiabetes rats:the blood glucose level reduced significantly among the low-dose columbin group,high-dosecolumbingroup,metformingroup,andDMcontrolgroupinthe0h,0.5h,1.0hand2.0h(p<0.05).The blood total cholesterol (TC) and triglycerides (TG) in the low-dose columbingroup, high-dose columbin group, metformin group were lower remarkably than the DMcontrol group (p<0.01). Compared with DM control group, free fatty acid (FFA) in thecolumbin group showed significant remarkerably reduction (p<0.01), metformin group reduced significantly (p<0.05).(2)Compared with the normal group, GLUT4 content in the DM control group reducedsignificantly (p<0.01). The GLUT4 content increased significantly among the low-dosecolumbin group, high-dose columbin group, metformin group (p<0.01).(3)KD of the insulin receptor (InsR) in the liver cell in the DM control was higher thannormal group (p<0.01). Bmax in the DM control group was higher than normal group(p<0.05). KD of IR in the liver cell in the all groups reduced significantly compared to theDM control group (p<0.01), Bmax reduced significantly in the high-dose columbin group,metformin group (p<0.05).Conclusion:(1) There was an anti-hyperglycemic effect of columbin in the type 2 diabetes ratsï¼›(2) Columbin increased GLUT4 content in the skeletal muscle Cell of type 2 diabetesratsï¼›(3)Columbin improved the binding affinity and capacity of the insulin receptor in thehepatocytic membrane of type 2 diabetes rats.
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