Liang Y, Cushman S M, Whitesell R R, Matschinsky F M
The Department of Biochemistry and Biophysics and Diabetes Research Center, University of Pennsylvania School of Medicine, Philadelphia 19104-6015, USA.
Horm Metab Res. 1997 Jun;29(6):255-60. doi: 10.1055/s-2007-979032.
GLUT2 may play an important role in pancreatic beta-cell glucose metabolism. A decrease in glucose uptake due to underexpression of GLUT2 has been considered as the cause of beta-cell dysfunction in diabetes with different pathogenesis. However, this view has been challenged by recent studies, in which the underexpression of GLUT2 was not accompanied by a decrease in glucose uptake. Our present aim is to evaluate the presumed importance of GLUT2 in maintaining the efficiency of beta-cell glucose uptake. We studied the kinetic characteristics of 3-O-methylglucose uptake in two beta-cell lines. One of these is the beta TC3 cell line which expresses GLUT1 and the other is the beta HC9 cell line which expresses both GLUT1 and GLUT2. Under equilibrium exchange conditions, 3-O-methylglucose transport in these two cell lines showed similar values of K(m) and V(max). The apparent IC50 of cytochalasin B for inhibiting 3-O-methylglucose transport in beta HC9 cells was nine times as high as in beta TC3 cells, indicating that GLUT1 is the critically important glucose transporter in the beta TC3 cell line and GLUT2 in the beta HC9 cell line. In both cell lines, the rates of glucose uptake were at least three times as fast as that of glucose phosphorylation. Our results suggest that GLUT1 is able to compensate for GLUT2 loss as it occurs in beta TC3 and maintains a commensurately high capacity of glucose uptake to sustain glucose metabolism in pancreatic beta-cells.
葡萄糖转运蛋白2（GLUT2）可能在胰腺β细胞的葡萄糖代谢中发挥重要作用。由于GLUT2表达不足导致的葡萄糖摄取减少被认为是不同发病机制的糖尿病中β细胞功能障碍的原因。然而，这一观点受到了最近研究的挑战，在这些研究中，GLUT2表达不足并未伴随着葡萄糖摄取的减少。我们目前的目的是评估GLUT2在维持β细胞葡萄糖摄取效率方面的假定重要性。我们研究了两种β细胞系中3 - O - 甲基葡萄糖摄取的动力学特征。其中一种是表达GLUT1的βTC3细胞系，另一种是同时表达GLUT1和GLUT2的βHC9细胞系。在平衡交换条件下，这两种细胞系中3 - O - 甲基葡萄糖的转运显示出相似的米氏常数（K(m)）和最大反应速度（V(max)）值。细胞松弛素B抑制βHC9细胞中3 - O - 甲基葡萄糖转运的表观半数抑制浓度（IC50）是βTC3细胞中的九倍，表明在βTC3细胞系中GLUT1是至关重要的葡萄糖转运蛋白，而在βHC9细胞系中GLUT2是至关重要的葡萄糖转运蛋白。在这两种细胞系中，葡萄糖摄取速率至少是葡萄糖磷酸化速率的三倍。我们的结果表明，GLUT1能够补偿βTC3细胞中发生的GLUT2缺失，并维持相应的高葡萄糖摄取能力以维持胰腺β细胞中的葡萄糖代谢。
