title: GLUT2 and glucokinase expression is coordinately regulated by sulfonylurea.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Porzio
authors.forename: L N
authors.initials: LN
authors.lastname: Marlier
authors.forename: M
authors.initials: M
authors.lastname: Federici
authors.forename: M L
authors.initials: ML
authors.lastname: Hribal
authors.forename: R
authors.initials: R
authors.lastname: Magnaterra
authors.forename: D
authors.initials: D
authors.lastname: Lauro
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: G
authors.initials: G
authors.lastname: Sesti
authors.forename: P
authors.initials: P
authors.lastname: Borboni
mesh_terms: 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
chemical_list: 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