M. Lachaal et al., HIGH K(M) OF GLUT-2 GLUCOSE-TRANSPORTER DOES NOT EXPLAIN ITS ROLE IN INSULIN-SECRETION, The American journal of physiology, 265(6), 1993, pp. 50000914-50000919
Evidence indicates that the high-K(m) GLUT-2 function of the islet cel
ls is essential for insulin secretion in response to glucose. To exami
ne possible significance of the high-K(m) transport function of GLUT-2
in this secretory response, we have studied by computer simulation th
e effects of high- and low-K(m) glucose uptake on the steady-state int
racellular glucose concentration and glucose phosphorylation in beta-c
ells. Our computations reveal that both the intracellular glucose conc
entration and the glucose phosphorylation catalyzed by glucokinase inc
rease significantly as the extracellular glucose concentration increas
es from 5 to 20 mM, even with a transport K(m) as low as 1.5 mM, the l
owest value known for GLUT-1. Our results indicate that the apparent r
equirement of GLUT-2 for glucose-sensitive insulin secretion cannot be
explained simply by its high-K(m) transport function alone and sugges
t that an isoform-specific, direct coupling of GLUT-2 with a certain g
lycolytic enzyme, such as glucokinase, is essential for the secretory
response.