ATP stimulates glucose transport through activation of P2 purinergic receptors in C(2)C(12) skeletal muscle cells.
Extracellular ATP acts as a signal that regulates a variety of cellular processes via binding to P2 purinergic receptors (P2 receptors). We herein investigated the effects and signaling pathways of ATP on glucose uptake in C(2)C(12) skeletal muscle cells. ATP as well as P2 receptor agonists (ATP-gamma S) stimulated the rate of glucose uptake, while P2 receptor antagonists (suramin) inhibited the stimulatory effect of ATP, indicating that P2 receptors are involved. This ATP-stimulated glucose transport was blocked by specific inhibitors of Gi protein (pertusiss toxin), phospholipase C (U73122), protein kinase C (GF109203X), and phosphatidylinositol (PI) 3-kinase (LY294002). ATP stimulated PI 3-kinase activity and P2 receptor antagonists blocked this activation. In C(2)C(12) myotubes expressing glucose transporter GLUT4, ATP increased basal and insulin-stimulated glucose transport. Finally, ATP facilitated translocation of GLUT1 and GLUT4 into plasma membrane. These results together suggest that cells respond to extracellular ATP to increase glucose transport through P2 receptors.
Kim
Min Suk
MS
Department of Biochemistry, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-ku, Seoul 130-701, Republic of Korea.
Lee
Jinhwa
J
Ha
Joohun
J
Kim
Sung Soo
SS
Kong
Yoon
Y
Cho
Yong Ho
YH
Baik
Hyung Hwan
HH
Kang
Insug
I
D016475:3T3 Cells; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000255:Adenosine Triphosphate; D002118:Calcium; D003847:Deoxyglucose; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005947:Glucose; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D020928:Mitogen-Activated Protein Kinases; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D018048:Receptors, Purinergic P2; D010738:Type C Phospholipases; D048051:p38 Mitogen-Activated Protein Kinases; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse