HUMAN GLUT-2 OVEREXPRESSION DOES NOT AFFECT GLUCOSE-STIMULATED INSULIN-SECRETION IN MIN6 CELLS

Accumulated evidence suggests that GLUT-2, in addition to its role in glucose transport, may also have other functions in glucose-stimulated insulin secretion. As a first step in addressing this possibility, we have engineered MING cells overexpressing human GLUT-2 by transfection with human GLUT-2 cDNA. Stable transformants harboring human GLUT-2 cDNA exhibited an approximately twofold increase in 3-O-methyl-D-glucose uptake at 0.5 and 15 mM. Glucokinase activity or glucose utilization measured by conversion of [5-H-3]glucose to [H-3]H2O was not, however, altered in the MlN6 cells overexpressing human GLUT-2. Furthermore, glucose-stimulated insulin secretion was not affected by overexpression of human GLUT-2. An abundance of GLUT-2, therefore, does not correlate with the glucose responsiveness of cells in which glycolysis is regulated at the glucose phosphorylating step. These data suggest that GLUT-2 by itself does not have significant functions other than its role in glucose transport in glucose sensing by MIN6 cells.