Insulin signaling after exercise in insulin receptor substrate-2-deficient mice.
The period immediately after exercise is characterized by enhanced insulin action in skeletal muscle, and on the molecular level, by a marked increase in insulin-stimulated, phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase activity. Because the increase in PI 3-kinase activity cannot be explained by increased insulin receptor substrate (IRS)-1 signaling, the present study examined whether this effect is mediated by enhanced IRS-2 signaling. In wild-type (WT) mice, insulin increased IRS-2 tyrosine phosphorylation (approximately 2.5-fold) and IRS-2-associated PI 3-kinase activity (approximately 3-fold). Treadmill exercise, per se, had no effect on IRS-2 signaling, but in the period immediately after exercise, there was a further increase in insulin-stimulated IRS-2 tyrosine phosphorylation (approximately 3.5-fold) and IRS-2-associated PI 3-kinase activity (approximately 5-fold). In IRS-2-deficient (IRS-2(-/-)) mice, the increase in insulin-stimulated, phosphotyrosine-associated PI 3-kinase activity was attenuated as compared with WT mice. However, in IRS-2(-/-) mice, the insulin-stimulated, phosphotyrosine-associated PI 3-kinase response after exercise was slightly higher than the insulin-stimulated response alone. In conclusion, IRS-2 tyrosine phosphorylation and associated PI 3-kinase activity are markedly enhanced by insulin in the immediate period after exercise. IRS-2 signaling can partially account for the increase in insulin-stimulated phosphotyrosine-associated PI 3-kinase activity after exercise.
Howlett
Kirsten F
KF
Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Sakamoto
Kei
K
Hirshman
Michael F
MF
Aschenbach
William G
WG
Dow
Matthew
M
White
Morris F
MF
Goodyear
Laurie J
LJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003847:Deoxyglucose / Q000493:pharmacokinetics; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D014443:Tyrosine; D006003:Glycogen; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases