de Vargas L M, Sobolewski J, Siegel R, Moss L G
Department of, New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
J Biol Chem. 1997 Oct 17;272(42):26573-7. doi: 10.1074/jbc.272.42.26573.
Insulin production by the pancreatic islet is tightly coupled to the concentration of blood glucose. The mechanism by which glucose controls proinsulin biosynthesis in beta cells is poorly understood. Analysis of insulin gene expression in individual cells within whole, living islets using adenovirus gene transfer and direct observation of insulin promoter-directed green fluorescent protein activity indicates that beta cells are functionally heterogeneous. An increase in glucose concentration not only stimulates expression within individual beta cells, but unexpectedly acts to increase the total number of positive cells. The net islet response to a given glucose stimulus reflects an integrated action of beta cells with individually differing behaviors. This additional level of functional complexity may provide new insights into the pathophysiology and treatment of diabetes mellitus.
胰岛产生胰岛素与血糖浓度紧密相关。葡萄糖调控β细胞中胰岛素原生物合成的机制目前仍知之甚少。利用腺病毒基因转移技术以及对胰岛素启动子驱动的绿色荧光蛋白活性进行直接观察，对完整活胰岛内的单个细胞中的胰岛素基因表达进行分析，结果表明β细胞在功能上具有异质性。葡萄糖浓度的升高不仅会刺激单个β细胞内的表达，而且出乎意料的是，还会增加阳性细胞的总数。胰岛对给定葡萄糖刺激的净反应反映了行为各异的β细胞的综合作用。这种功能复杂性的额外层面可能为糖尿病的病理生理学和治疗提供新的见解。
