CAJ | 학술논문

目的通过观察肌腱膜纤维肉瘤肿瘤基因同系物A(MafA)基因杂合子小鼠在胰岛素分泌、相关基因表达、血糖及血清胰岛素水平等方面的变化,探讨MafA基因在青少年起病的成人型糖尿病(MODY)发生中的作用.方法将动物分为MafA杂合子组及野生(C57 BL/6J)对照组,采用腹腔葡萄糖耐量实验(IPGTT)观察杂合子小鼠血糖经时分布曲线及血清胰岛素的变化;胰岛素耐量实验了解两组动物对胰岛素的敏感性;半定量PCR法检测杂合子小鼠MafA、胰岛素以及PdX1和Beta2等基因的表达水平;组织免疫荧光法观察胰腺中胰岛的组织形态并进行α、β细胞计数分析.结果 (1) MafA杂合子小鼠在生后2周开始呈现血糖增高及体重减轻、胰岛素分泌明显下降(P＜0.05或P＜0.01),胰岛素敏感性未发生明显改变.(2) MafA杂合子小鼠胰岛体积较对照组明显增大,但胰腺细胞数量、α、β细胞的分布形态及比值无明显变化.(3)半定量PCR结果显示,与对照组相比,MafA杂合子小鼠MafA基因、胰岛素基因、Beta 2基因表达水平均明显降低(均P＜0.05),而胰高血糖素及Pdxl水平没有变化.结论 MafA基因杂合子小鼠在出生早期即表现为血糖升高、体重减轻、胰岛素产生能力下降等.MafA基因的表达对糖尿病的发生起重要作用.该基因可能是一种新的MODY致病基因.
목적 통과관찰기건막섬유육류종류기인동계물A(MafA)기인잡합자소서재이도소분비、상관기인표체、혈당급혈청이도소수평등방면적변화,탐토MafA기인재청소년기병적성인형당뇨병(MODY)발생중적작용.방법 장동물분위MafA잡합자조급야생(C57 BL/6J)대조조,채용복강포도당내량실험(IPGTT)관찰잡합자소서혈당경시분포곡선급혈청이도소적변화;이도소내량실험료해량조동물대이도소적민감성;반정량PCR법검측잡합자소서MafA、이도소이급PdX1화Beta2등기인적표체수평;조직면역형광법관찰이선중이도적조직형태병진행α、β세포계수분석.결과 (1) MafA잡합자소서재생후2주개시정현혈당증고급체중감경、이도소분비명현하강(P＜0.05혹P＜0.01),이도소민감성미발생명현개변.(2) MafA잡합자소서이도체적교대조조명현증대,단이선세포수량、α、β세포적분포형태급비치무명현변화.(3)반정량PCR결과현시,여대조조상비,MafA잡합자소서MafA기인、이도소기인、Beta 2기인표체수평균명현강저(균P＜0.05),이이고혈당소급Pdxl수평몰유변화.결론 MafA기인잡합자소서재출생조기즉표현위혈당승고、체중감경、이도소산생능력하강등.MafA기인적표체대당뇨병적발생기중요작용.해기인가능시일충신적MODY치병기인.
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.