ATP stimulates glucose transport through activation of P2 purinergic receptors in C(2)C(12) skeletal muscle cells

• Published in: Archives of biochemistry and biophysics 2002-05, Vol.401 (2), p.205-214
• Main Authors: Kim, Min Suk, Lee, Jinhwa, Ha, Joohun, Kim, Sung Soo, Kong, Yoon, Cho, Yong Ho, Baik, Hyung Hwan, Kang, Insug
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adenosine Triphosphate - pharmacology; Animals; Biological Transport, Active - drug effects; Calcium - metabolism; Cell Line; Deoxyglucose - metabolism; Glucose - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 4; GTP-Binding Protein alpha Subunits, Gi-Go - antagonists & inhibitors; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Insulin - pharmacology; Mice; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Receptors, Purinergic P2 - drug effects; Receptors, Purinergic P2 - metabolism; Signal Transduction; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism
• ISSN: 0003-9861

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.