GLUT2 and glucokinase expression is coordinately regulated by sulfonylurea.
In the present study we examined the effect of sulfonylurea on the expression of the glucose transporter GLUT2 and the glucose phosphorylating enzyme Glucokinase (GK) in betaTC6-F7 cells; furthermore, we studied the modifications induced by sulfonylurea on glucose-responsiveness and -sensitivity. Results 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 are coordinately regulated by sulfonylurea, probably by a common mechanism. Glucose-induced insulin release is increased by sulfonylurea as well as glucose 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 would explain the reduced insulin secretion occurring after chronic sulfonylurea treatment.
Porzio
O
O
Department of Internal Medicine, University of Rome Tor Vergata, Italy.
Marlier
L N
LN
Federici
M
M
Hribal
M L
ML
Magnaterra
R
R
Lauro
D
D
Fusco
A
A
Sesti
G
G
Borboni
P
P
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D005941:Glucokinase / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005941:Glucokinase; D005947:Glucose