| Objective:To investigate the effects of exenatide on GLP-1 secretion and expression of GLP-1 receptors in rat islets with different diabetic course,and to explore the related mechanism.Method:The rats were randomly divided into normal control group and diabetic model groups that included the 2 weeks intervention group of exenatide?the 4 weeks intervention group of exenatide?the 8 weeks intervention group of exenatide.The diabetic model groups were fed on high-fat and sugar diet,while the normal control group was fed on normal diet. Exenatide was subcutaneously injected in the 8 weeks intervention group at the beginning experiment,the 4 weeks intervention group was subcutaneously injected after 4 weeks and the 2 weeks intervention group was subcutaneously injected after 1 week of the diabetic model establishment. Exenatide was subcutaneously injected at the dosage of 5ug/kg twice a day. Measure the level of GLP-1 by ELISA method and GLP-1R by immunohistochemical method after 8 weeks of observation of the rat weight and the levels of blood glucose.Results:The weight of the 8 weeks intervention group was lower than the normal control group?the 4 weeks intervention group?the 2 weeks intervention group at the end of the fourth week of the experiment,P<0.05.At the end of the eighth week of the experiment, the weight of the diabetic model groups was lower than the normal group for the effects of the model establishment, P<0.05.The weight of the 8 weeks intervention group was lower than the 4 weeks intervention and the 2 weeks intervention at the end of the eighth week,P<0.05.The levels of the fasting plasma glucose in the 8 weeks intervention group were lower than in the normal control group?in the 4 weeks intervention group?in the 2 weeks intervention group at the end of the fourth week,P<0.05.There was no significant difference of the 2h postload glucose levels between the 8 weeks intervention group and the normal control group at the end of the fourth week,P>0.05.The 2h postload glucoselevels in the 8 weeks group and the normal control group were lower than in the 4 weeks group and in the 2 weeks group at the end of the fourth week,P<0.05.The levels of the fasting plasma glucose and the 2h postload glucose in the normal control group were lower than in the all intervention groups of exenatide at the end of the eighth week, P<0.05.There was no significant difference of the levels of the fasting plasma glucose and the levels of the 2h postload glucose among all intervention groups of exenatide at end of the eighth week,P>0.05.The variation of the postprandial glucose levels at five time points shows a great difference among all groups at the end of the eighth week,P<0.05.The AUC values in the normal control group were lower than in the diabetic model groups at the end of eighth week,P<0.05.The AUC values in the 8 week intervention group were lower than in the 2 week intervention group at the end of the eighth week,P<0.05.There was no significant difference of the GLP-1 secretion levels among all groups, P>0.05.There was no significant difference of the islet numbers in the low-power field between the normal control group and the 8 week intervention group,P>0.05. In the low-power field, the islet numbers in the normal control group and in the 8 week intervention group were more than in the 4 week intervention group, P<0.01;the islet numbers in the 4 week intervention group were more than in the 2 week intervention group, P<0.01.The OD values of the GLP-1R in normal control group were higher than in the 8 week intervention group, P<0.01;The OD values of the GLP-1Rin the 8 week intervention group were higher than in the 4 week intervention group,P<0.01;The OD values of the GLP-1Rin the 4 week intervention group were higher than in the 2 week intervention group,P<0.01.Conclusion:(1)Exenatide reducedthe diabetic rat weight,and the weight loss from early intervention was more than from the late intervention.(2)Exenatide decreased the AUC values of the postprandial glucose levels in the diabetic rat,and the reduction in the early intervention group was more than in the late intervention group.(3)Exenatide increased the GLP-1 receptors expression in the diabetic rat islet,and the results in the early intervention were more significant than in the late intervention.(4)There were no significant difference of the Exenatide effects on GLP-1 secretion in diabetic rat.(5)Exenatide promoted the islet proliferation of the diabetic rat, and the results in the early intervention were more significant than in the late intervention. |
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