ABSTRACT
Objective To clarify the role of MafA gene in development of MODY (maturity onset diabetes of the young) by studying insulin production,gene expression,and serum glucose level in heterozygous MafA gene knockout mice.Methods C57BL/6J mice were used as control animals,MafA gene heterozygous mice were analyzed.The distribution curve of blood sugar levels over time and serum insulin of heterozygous mice were determined by using IPGTT.The sensitivity of the mice to insulin was examined by injecting insulin assay.The expression levels of genes of MafA,insulin,pdX1,Beta2,and other genes of heterozygous mice were analyzed by semi-quantitative RT-PCR.Morphological changes in pancreatic tissue and α-and β-cell counts were obtained by using immunofluorescence/histological examination.Results (1) Two weeks after birth,MafA gene heterozygous mice began to show that the blood glucose level was increased,weight was reduced,and the amount of insulin secretion was clearly decreased (P＜0.05 or P＜0.01) while the insulin sensitivity did not change significantly.(2)The islet volume in MafA gene heterozygous mice was increased significantly as compared with the control group.However there were no significant changes in the number of pancreatic cells,distribution patterns,and the ratio of α and β cell.(3) Semi-quantitative RT-PCR detection showed that,compared with the control group,MafA gene level,the amount of insulin and Beta2 gene in MafA gene heterozygous mice were significantly reduced(all P＜0.05),while no changes in the amount of glucagons and level of Pdx1 were found.Conclusions The blood glucose level of MafA gene heterozygous mice was raised early after birth.MafA gene is likely to be a new disease ralated gene of MODY.
ABSTRACT
Objective To study the effect of the MafA therapy for blood slucose control in diabetic rats.Methods Rats were divided into 3 groups:treatment group,DM group and control group.In DM group,Wistar rats were rendered diabetic by intrvenous injection of streptozotocin(STZ).In treatment group,mixture of MafA and liposomes at the volume ratio of 1:1 was injected to the portal vein of the diabetic rats.Blood glucose change in the diabetic rats Was measured.Results ① For treatment group,blood slucose decreased from 20.6 mmol/L-22.8 mmol／L to 13.6 mmol／L-14.8 mmol／L and plasma insulin level was significantly elevated for a duration about 2 weeks.②After treatment,blood slucose level significantly decreased compared to DM group (P<0.05).③ Plasma insulin level Was significantly higher than that in DM group(P<0.05).④ Expression of MafA mRNA can be detected in the liver oftreatment group while it Was not found in DM group.Immunohistochemical analysis revealed that insulin expression Was found in the liver of treatment group while it Was not found in the liver of DM group.Conclusion Injection of MafA and liposomes at the volume ratio of 1:1 via the portal vein can effectively decrease blood glucose in diabetic rats.