GLUT2 and glucokinase expression is coordinately regulated by sulfonylurea

In the present study we examined the effect of sulfonylurea on the expressi on of the glucose transporter GLUT2 and the glucose phosphorylating enzyme Glucokinase (GK) in beta TC6-F7 cells; furthermore, we studied the modifica tions induced by sulfonylurea on glucose-responsiveness and -sensitivity. R esults demonstrate that sulfonylurea increases GLUT2 and GK mRNA expression after 24 h in a dose-dependent manner. On the contrary, after 48 and 72 h a time-dependent reduction of both GLUT2 and GK mRNA. occurs. GLUT2 and GK protein expression follow the same modifications. Therefore, GLUT2 and GK a re coordinately regulated by sulfonylurea, probably by a common mechanism. Glucose-induced insulin release is increased by sulfonylurea as well as glu cose sensitivity. Our study suggests that short-term effect of sulfonylurea increases while long-term effect reduces the expression of glucose sensing elements. The long-term inhibitory effect on glucose sensing elements woul d explain the reduced insulin secretion occurring after chronic sulfonylure a treatment. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.