Effect Of Glucagon-like Peptide-1(GLP-1)on MafA-deficient Mice

Objective:To investigate effect of glucagon-like peptide-1（GLP-1）on MafA-deficient mice.Materials and Methods:Ten 6-week-old male MafA knockout mice were selected and randomly divided into 2 groups of 5 mice each.Ten ICR wild-type mice of the same age were randomly divided into two groups of five.GLP-1 or physiological saline（50μg/kg body weight）was given to the four groups,one kind for each group twice a day for 4weeks.The grouping is as follows:MafA knockout mice:MafA^-/-GLP-1 group,MafA^-/-saline group;ICR wild-type mice:wild GLP-1 group,wild saline group.Record of blood glucose level and body weight were kept in each group;and immunohistochemical sections were used to count and analyze the number of isletαcells andβcells in each experimental group,theβcells/αcells ratio was calculated,and the Real-time fluorescence quantitative PCR flurogenic quantitative polymerase chain Reaction（FQ-PCR）was applied to analyze the changes of related transcription factors Pdx-1,FoxO1,and insulin I and so on.Results:In the absence of MafA gene,compared with MafA^-/-saline group,the blood glucose level of MafA^-/-GLP-1 group was significantly improved,and the difference was statistically significant（p<0.01）;indicators notes obvious decline in food intake and loss of weight（p<0.05）;while for the pancreas sections,β/αcells ratio is increased（2.25±0.22/2.67±0.37）,which is considered statistically significant with（p<0.05）.By real-time fluorescence quantitative PCR,it was found that PDX-1mRNA in MafA^-/-GLP-1 group was significantly increased（p<0.01）;FoxO1mRNA level decreased significantly（p<0.05）Conclusions:1.GLP-1 can significantly improve blood glucose levels in MafA knockout mice.2.GLP-1 can reduce food intake and body weight of MafA knockout mice.3.GLP-1 is possible to increase the regeneration ofβcells by inducing PDX-1and then promotingαcells to isletβcellstransdifferentiation,or through reversion of dedifferentiation of isletβcells by inhibiting FoxO1.