Regulation of glucose transporter 1 expression by gliclazide in rat L6 myoblasts.
Sulphonylureas are known to enhance insulin secretion from the pancreas and its sensitivity of the extrapancreatic target organs. In this study, we clarified a direct extrapancreatic effect of the sulphonylureas and of gliclazide, on the glucose transport system in cultured rat L6 myoblasts, which predominantly expressed glucose transporter 1 (GLUT 1). Our results show that gliclazide stimulated 2-deoxy-[3H]-D-glucose (2DG) uptake, 24 h after treatment, in a dose-dependent manner, and it also increased GLUT 1 protein synthesis and mRNA expression; 2DG uptake and GLUT 1 protein synthesis induced by gliclazide were completely blocked by protein kinase A (PKA) inhibitors (H89 and rp-cAMP), and gliclazide increased the intracellular cAMP levels 3 to 24 hr after the treatment. These results show that in rat L6 myoblasts, gliclazide stimulates glucose transport activity by the induction of GLUT 1 gene expression through PKA.
Imamur
H
H
Department of Internal Medicine, Niigata Rosai Hospital, Japan. 630tanuki128-826@jcom.home.ne.jp
Morimoto
I
I
Tanaka
Y
Y
Hashimoto
O
O
Kanda
K
K
Yamashita
S
S
Eto
S
S
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005907:Gliclazide / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics*; D009132:Muscles / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014316:Tritium
D004791:Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D014316:Tritium; D003847:Deoxyglucose; D017868:Cyclic AMP-Dependent Protein Kinases; D005907:Gliclazide