Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Goodyear, Laurie J., Pi-Yun Chang, Daniel J. Sherwood, Scott D. Dufresne, and David E. Moller. Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, the Department of Medicine, Beth Israel Hospital, Boston, MA 02215, and the Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ 07065
APStracts 3:0099E, 1996.
Studies in mammalian cells have established the existence of at least 3 distinct mitogen-activated protein kinase (MAP kinase) signaling pathways that are activated by a variety growth factors and/or environmental stressors. We determined if physical exercise, a physiological stressor, and insulin, a metabolic stimulator and growth factor, activate the c-jun NH2 terminus kinase (JNK), p38 kinase, and/or the extracellular regulatory kinases (p42MAPK, p44MAPK, or ERKs) signaling pathways in rat skeletal muscle. Animals were studied immediately after running on a motorized treadmill for 10 to 60 min (20 m/min, 10% grade), or 5 to 30 min following an intraperitoneal injection of insulin (20 U/rat). Exercise increased skeletal muscle JNK activity by 2- to 3-fold throughout the time course studied, whereas insulin did not significantly increase JNK activity. p38 activity was slightly stimulated by exercise and not by insulin. The ERK kinase pathway, as assessed by RSK2 activity assays and phospho-specific ERK1/ERK2 immunoblotting, was stimulated by both exercise and insulin. These data are the first demonstration of exercise stimulating multiple intracellular signaling pathways in skeletal muscle. Activation of these MAP kinase signaling pathways may mediate changes in skeletal muscle growth and metabolism that occur in response to exercise.

Received 28 March 1996; accepted in final form 3 May 1996.
APS Manuscript Number E156-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96