HIGH K(M) OF GLUT-2 GLUCOSE-TRANSPORTER DOES NOT EXPLAIN ITS ROLE IN INSULIN-SECRETION

Evidence indicates that the high-K(m) GLUT-2 function of the islet cells is essential for insulin secretion in response to glucose. To examine possible significance of the high-K(m) transport function of GLUT-2 in this secretory response, we have studied by computer simulation the effects of high- and low-K(m) glucose uptake on the steady-state intracellular glucose concentration and glucose phosphorylation in beta-cells. Our computations reveal that both the intracellular glucose concentration and the glucose phosphorylation catalyzed by glucokinase increase significantly as the extracellular glucose concentration increases from 5 to 20 mM, even with a transport K(m) as low as 1.5 mM, the lowest value known for GLUT-1. Our results indicate that the apparent requirement of GLUT-2 for glucose-sensitive insulin secretion cannot be explained simply by its high-K(m) transport function alone and suggest that an isoform-specific, direct coupling of GLUT-2 with a certain glycolytic enzyme, such as glucokinase, is essential for the secretory response.