Class II phosphoinositide 3-kinase is activated by insulin but not by contraction in skeletal muscle.
While the role of the class IA phosphoinositide 3-kinase (PI 3-kinase) in insulin signaling is well established, little is known about the role of the class II PI 3-kinases. We show that insulin stimulation of intact rat soleus and epitrochlearis muscles causes a 3- to 4-fold increase in the activity of the wortmannin-resistant alpha isoform of the class II PI 3-kinase (PI3K-C2alpha). This activation is rapid and parallels the insulin-induced activation of the class IA PI 3-kinase associated with IRS-1 in these muscles. However, while contraction activated p38 Map kinase, it did not stimulate the activity of the class II PI 3-kinase. Therefore, activation of class II PI 3-kinase is unlikely to provide a mechanism that explains the fact that exercise-induced activation of glucose uptake is not blocked by wortmannin. However, the results suggest that activation of class II PI 3-kinase is likely to play a role in insulin signaling pathways in skeletal muscle.
Soos
M A
MA
Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Jensen
J
J
Brown
R A
RA
O'Rahilly
S
S
Shepherd
P R
PR
Whitehead
J P
JP
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077191:Wortmannin