Establishment Of OGA Specific Knockout Mice In Pancreatic Beta Cells And Its Effect Influence Of Sugar Metabolism

Objective To establish pancreatic β cell-specific knockout of OGA(Pancreatic cell-specific knockout of OGA,OGA β cell KO)were observed in mice.Under the conditions of no induction and high fat diet,the influence of pancreatic βcell-specific knockout of OGA on glucose metabolism were observed.Method 1.The OGA beta cell KO mouse model was constructed by Cre-Lox P recombinant enzyme system and the model were verified by IHC(immunohistochemistry,IHC)2.With NCD(Normal Chow diat,NCD)feeding conditions,monitoring the FBW(Fasted body weight,FBW)and FBG(Fasted blood glucose,FBG)of OGA beta cell KO mice and WT(Wild type WT)mice weekly。By detecting the Intraperitoneal glucose tolerance test(IPGTT),Intraperitoneal insulin tolerance test(IPITT)and fasting serum insulin to observe the effect of pancreatic beta cell OGA deletion on glucose homeostasis and insulin sensitivity3.With high fat diet(high-fat,diet,HFD)feeding conditions,evaluation of the influence of pancreatic beta cell OGA deletion to induced by HFD on glucose metabolism in mice by detecting the IPITT,IPGTT and fasting serum insulin level;two groups in islet insulin secretion by immunofluorescence staining of paraffin sections and the islets cell apoptosis by DAB TUNEL staining were observed 4.Analysis of 16 S intestinal microbial sequencing of feces of KO and WT mice fed on high-fat diets respectivelyResults 1.Our group successfully constructed the first pancreatic β cell knockout of OGA mice of the world.2.No significant difference of fasting body mass and fasting blood glucose in KO and WT mice with normal diet were detected weekly.The results of IPGTT showed that the glucose tolerance decreased significantly of OGA β cell KO mice compared with WT mice and the male mice decreased significantly than the female;The results of IPITT showed that the Pancreatic β cells OGA deletion could reduce the insulin sensitivity of male mice,and there was no significant difference in the content of fasting insulin in two groups.3.Compared with WT mice,the fasting blood glucose of β cells OGA deletion was significantly higher in the high fat diet group;the impaired glucose tolerance level of the high fat diet OGA deletion mice was significantly higher than the other groups,and the insulin sensitivity was significantly reduced.Compared with WT mice,the fasting insulin is lower than that in the HFD OGA deletion mice;the result of paraffin section immunofluorescence staining showed that the insulin secretion decreased in the β cells OGA KO mice fed by HFD;DAB TUNEL staining shows the number of apoptotic cells in the β cells OGA KO mice.4.The intestinal bacterial operational taxonomic units(OTU)of OGA KO mice was decreased,A/F and F/B value were decreased,the amount of beneficial bacteria such as Lactobacillus were decreased。Conclusion: The level of O-GlcNAc glycosylation in pancreatic β cells after OGA knockout is increased,resulting in impaired glucose tolerance and insulin sensitivity in KO mice.Meanwhile,pancreatic β cells after OGA knockout can Increase the disorder of glucose metabolism induced by high fat diet.The lack of OGA can reduce intestinal species abundance,reduce the number of probiotics.It can be seen that the deletion of OGA in pancreatic β cells may affect the homeostasis of glucose metabolism.This discovery provides new ideas for the search for new targets for the treatment of glucose metabolism disorders.