Inhibition of the high-affinity glucose transporter GLUT 1 affects the sensitivity to glucose in a hamster-derived pancreatic beta cell line (HIT) |
| |
Authors: | A M Rabuazzo M Buscema C Vinci V Caltabiano M Anello R Vigneri Dr F Purrello |
| |
Institution: | (1) Institute of Internal Medicine, Metabolism and Endocrinology, University of Catania Medical School, Catania, Italy;(2) Cattedra di Endocrinologia, Ospedale Garibaldi, Piazza S. Maria di Gesù, I-95123 Catania, Italy |
| |
Abstract: | Summary HIT is a hamster-derived beta-cell line which in contrast to normal beta cells that only express the high Km GLUT-2 glucose transporter, also expresses the low Km glucose transporter GLUT 1. In HIT cells the abnormal glucose transport mechanism is associated with a marked shift to the left of the glucose-induced insulin release dose-response curve. We have used this cell model to investigate whether changes in glucose transport affect the glucose-induced insulin release. HIT cells were first incubated with a concentration of cytochalasin B (0.4 mol/l) that selectively inhibits the GLUT-1 but not the GLUT-2 transporter. The consequences of blocking glucose phosphorylation and insulin release were studied. Exposure to 0.4 mol/l cytochalasin B for 1 h caused a selective loss of the low Km transport: the calculated Vmax of GLUT 1 was reduced from 1726±98 to 184±14 pmol · mg protein–1 5 min–1 (mean±SEM, n=6, p<0.005), while no major difference in the high Km (GLUT-2) transport was observed. In cytochalasin B exposed HIT cells the glucose phosphorylating activity (due to hexokinase and glucokinase) was unaffected. In these cells, however, the dose-response curve of glucose-induced insulin release was significantly shifted to the right: the 50% of maximal response (increment over baseline) was reached at an average glucose concentration of 2.9±0.2 mmol/l (vs 0.6±0.01 mmol/l in control HIT cells mean±SE, n=5, p<0.05) and the maximal effect was reached at 11.0 mmol/l glucose (vs 2.8 mmol/l in control HIT cells p<0.005). These results are consistent with the hypothesis that the affinity of the glucose transport system may contribute to determination of the glucose threshold concentration that triggers insulin secretion. |
| |
Keywords: | GLUT 1 GLUT 2 glucokinase glucose sensitivity insulin release HIT cells |
本文献已被 SpringerLink 等数据库收录! |
|