| Objective: Our former studies showed that Calcium/calmodulin-dependent serine protein kinase(CASK)is highly expressed in islet β cells and participates in the process of insulin secretion.However,the effect of CASK on islet β-cell function and in T2 DM is not fully understood.In the present study,the conditional islet β-cell CASK gene knockout(βCASK KO)mice model was utilized to investigate the function of CASK in islet β cells and its effect on Glycometabolism.Methods: 1.Conditional islet β cell CASK knockout mice was constructed by using Cre-loxp gene targeting system and tamoxifen;2.Metabolic phenotypic analysis of normal diet βCASK KO mouse;3.Establishment of high fat Diet-induced type 2diabetes model mice;4.Metabolic phenotypic analysis of high-fat diet βCASK KO mouse.Results: 1.Western blot,q PCR and immunofluorescence experiments was used to confirme that the conditional islet β cell CASK knockout mice were successfully constructed;2.There was no significant difference between body weight,blood glucose,glucose tolerance,insulin sensitivity,serum insulin level,β-cell insulin secretion and islet size in the βCASK KO mouse and the control mouse under normal diet feeding.3.Under high-fat diet feeding,the body weight,blood glucose,serum insulin level and other results suggest that the model of T2 DM mice is successful;4.Under high-fat diet feeding,the blood glucose of βCASK KO mouse was lowered,glucose tolerance was improved,insulin sensitivity was increased,and hyperinsulinemia was relieved compared with the control mouse.Conclusion: 1.Knockout of CASK has no effect on body weight,blood glucose,glucose tolerance,insulin sensitivity,insulin secretion and insulin synthesis under normal diet feeding;2.Knocking out of CASK has no effect on insulin and glucagon content and islet morphology under normal diet feeding;3.Knocking out of CASK can alleviate hyperlipidemia,glucose tolerance impaired,insulin resistance,hyperglycaemia under high-fat diet feeding. |
PDF Full Text Request