High Km of GLUT-2 glucose transporter does not explain its role in insulin secretion.
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.
Lachaal
M
M
Biophysics Laboratory, Veterans Affairs Medical Center, Buffalo, New York.
Spangler
R A
RA
Jung
C Y
CY
D000818:Animals; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010766:Phosphorylation
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005941:Glucokinase; D005947:Glucose