AJP - Endocrinology and Metabolism, Vol 265, Issue 6 E914-E919, Copyright © 1993 by American Physiological Society
High Km of GLUT-2 glucose transporter does not explain its role in insulin secretion
M. Lachaal, R. A. Spangler and C. Y. Jung
Biophysics Laboratory, Veterans Affairs Medical Center, Buffalo, New York.
Evidence indicates that the high-Km GLUT-2 function of the islet cells is
essential for insulin secretion in response to glucose. To examine possible
significance of the high-Km transport function of GLUT-2 in this secretory
response, we have studied by computer simulation the effects of high- and
low-Km 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 Km 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-Km 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.
