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Insulin signaling after exercise in insulin receptor substrate-2-deficient mice

journal contribution
posted on 2002-02-01, 00:00 authored by Kirsten HowlettKirsten Howlett, K Sakamoto, M Hirschman, W Aschenbach, M Dow, M White, L Goodyear
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 (2.5-fold) and IRS-2-associated PI 3-kinase activity (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 (3.5-fold) and IRS-2-associated PI 3-kinase activity (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.

History

Journal

Diabetes

Volume

51

Issue

2

Pagination

479 - 483

Publisher

American Diabetes Association

Location

New York, N.Y.

ISSN

0012-1797

eISSN

1939-327X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2002 by the American Diabetes Association, Inc.