A diacylglycerol kinase inhibitor, R59022, stimulates glucose transport through a MKK3/6-p38 signaling pathway in skeletal muscle cells.
Diacylglycerol kinase (DGK) is one of lipid-regulating enzymes, catalyzes phosphorylation of diacylglycerol to phosphatidic acid. Because skeletal muscle, a major insulin-target organ for glucose disposal, expresses DGK, we investigated in the present study a role of DGK on glucose transport in skeletal muscle cells. PCR study showed that C2C12 myotubes expressed DGKalpha, delta, epsilon, zeta, or theta isoform mRNA. R59022, a specific inhibitor of DGK, significantly increased glucose transport, p38 and MKK3/6 activation in C2C12 myotubes. The R59022-induced glucose transport was blocked by SB203580, a specific p38 inhibitor. In contrast, R59022 failed to stimulate both possible known mechanisms to enhance glucose transport, an IRS1-PI3K-Akt pathway, muscle contraction signaling or GLUT1 and 4 expression. All these results suggest that DGK may play a role in glucose transport in the skeletal muscle cells through modulating a MKK3/6-p38 signaling pathway.
Takahashi
Nobuhiko
N
Department of General Medicine, Asahikawa Medical College, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. ntkhs@asahikawa-med.ac.jp
Nagamine
Miho
M
Tanno
Satoshi
S
Motomura
Wataru
W
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D048371:MAP Kinase Kinase 3 / Q000378:metabolism*; D048669:MAP Kinase Kinase 6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011744:Pyrimidinones / Q000008:administration & dosage*; D013844:Thiazoles / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D011744:Pyrimidinones; D013844:Thiazoles; C047505:R 59022; D019852:Diacylglycerol Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C482531:Map2k3 protein, mouse; C482567:Map2k6 protein, mouse; D005947:Glucose