Heimberg H, De Vos A, Moens K, Quartier E, Bouwens L, Pipeleers D, Van Schaftingen E, Madsen O, Schuit F
Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7036-41. doi: 10.1073/pnas.93.14.7036.
Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase.
葡萄糖激酶在肝细胞和胰腺β细胞中的表达对哺乳动物的葡萄糖稳态具有重要的生理意义。肝脏中的葡萄糖激酶催化葡萄糖代谢的第一步，而β细胞中的葡萄糖激酶催化葡萄糖调节胰岛素释放所需的限速步骤。本研究报道了葡萄糖激酶在受葡萄糖负调节的大鼠胰高血糖素分泌α细胞中的表达。纯化的大鼠α细胞表达葡萄糖激酶mRNA和蛋白质，其转录本长度、核苷酸序列和免疫反应性与β细胞亚型相同。葡萄糖激酶活性占α细胞提取物中葡萄糖磷酸化的50%以上，占完整细胞中葡萄糖利用的90%以上。产生胰高血糖素的肿瘤MSL-G-AN也含有葡萄糖激酶mRNA、蛋白质和酶活性。这些数据表明，葡萄糖激酶可能作为胰腺α细胞中的代谢性葡萄糖传感器，从而介导细胞外葡萄糖直接调节胰高血糖素释放的机制。由于这些细胞不表达Glut2，我们认为葡萄糖感应不一定需要Glut2和葡萄糖激酶的共表达。
