Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle.

We have examined the effects of insulin on p38 mitogen-activated protein kinase (MAPK) phosphorylation in human skeletal muscle and the effects of prior exercise hereon. Seven men performed 1-h one-legged knee extensor exercise 3 h before the initiation of a 100-min euglycemic-hyperinsulinemic (600 pmol/l) clamp. Glucose uptake across the legs was measured with the leg balance technique, and muscle biopsies were obtained from the rested and exercised vastus lateralis before and during insulin infusion. Net glucose uptake during the clamp was approximately 50% higher (P < 0.05) in the exercised leg than in the rested leg. Insulin induced a modest sustained 1.2- and 1.3-fold increase (P < 0.05) in p38 MAPK phosphorylation in the rested and exercised legs, respectively. However, p38 phosphorylation was approximately 50% higher (P < 0.05) in the exercised compared with the rested leg before and during insulin infusion. We conclude that a physiological concentration of insulin causes modest but sustained activation of the p38 MAPK pathway in human skeletal muscle. Furthermore, the stimulatory effect of exercise on p38 phosphorylation is persistent for at least 3 h after exercise and remains evident during subsequent insulin stimulation. Because p38 MAPK has been suggested to play a necessary role in activation of GLUT-4 at the cell surface, the present data may suggest a putative role of p38 MAPK in the increased insulin sensitivity of skeletal muscle after exercise.

[1]  J. Hawley,et al.  Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise , 2003, The Journal of physiology.

[2]  B. Ursø,et al.  Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise. , 2002, Diabetes.

[3]  J. Zierath,et al.  Evidence against high glucose as a mediator of ERK1/2 or p38 MAPK phosphorylation in rat skeletal muscle. , 2001, American journal of physiology. Endocrinology and metabolism.

[4]  R. Somwar,et al.  GLUT4 translocation precedes the stimulation of glucose uptake by insulin in muscle cells: potential activation of GLUT4 via p38 mitogen-activated protein kinase. , 2001, The Biochemical journal.

[5]  J. Zierath,et al.  Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream targets in human skeletal muscle , 2001, The Journal of physiology.

[6]  W. Derave,et al.  Glucose, exercise and insulin: emerging concepts , 2001, The Journal of physiology.

[7]  J. Zierath,et al.  Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction. , 2001, Acta physiologica Scandinavica.

[8]  Y. Gotoh,et al.  MKK6/3 and p38 MAPK Pathway Activation Is Not Necessary for Insulin-induced Glucose Uptake but Regulates Glucose Transporter Expression* , 2001, The Journal of Biological Chemistry.

[9]  L. Nolte,et al.  Mechanisms underlying impaired GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats. , 2000, American journal of physiology. Endocrinology and metabolism.

[10]  Jiahuai Han,et al.  Myogenic differentiation requires signalling through both phosphatidylinositol 3-kinase and p38 MAP kinase. , 2000, Cellular signalling.

[11]  R. Somwar,et al.  Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport. , 2000, Diabetes.

[12]  W. Derave,et al.  Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity. , 2000, American journal of physiology. Endocrinology and metabolism.

[13]  R. Fielding,et al.  Marathon running transiently increases c‐Jun NH2‐terminal kinase and p38γ activities in human skeletal muscle , 2000, The Journal of physiology.

[14]  B. Hansen,et al.  Insulin signaling and insulin sensitivity after exercise in human skeletal muscle. , 2000, Diabetes.

[15]  Jiahuai Han,et al.  Selective Activation of p38α and p38γ by Hypoxia , 1999, The Journal of Biological Chemistry.

[16]  Jiahuai Han,et al.  Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells. , 1999, The Journal of biological chemistry.

[17]  R. Somwar,et al.  An Inhibitor of p38 Mitogen-activated Protein Kinase Prevents Insulin-stimulated Glucose Transport but Not Glucose Transporter Translocation in 3T3-L1 Adipocytes and L6 Myotubes* , 1999, The Journal of Biological Chemistry.

[18]  L. Nolte,et al.  Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise. , 1998, Journal of applied physiology.

[19]  Hsien-yu Wang,et al.  Conditional, Tissue-specific Expression of Q205L Gαi2 in Vivo Mimics Insulin Activation of c-Jun N-terminal Kinase and p38 Kinase* , 1998, The Journal of Biological Chemistry.

[20]  W. Derave,et al.  Hypoxia and contractions do not utilize the same signaling mechanism in stimulating skeletal muscle glucose transport. , 1998, Biochimica et biophysica acta.

[21]  Yong Jiang,et al.  Characterization of the Structure and Function of the Fourth Member of p38 Group Mitogen-activated Protein Kinases, p38δ* , 1997, The Journal of Biological Chemistry.

[22]  B. Hansen,et al.  Insulin Signaling in Human Skeletal Muscle: Time Course and Effect of Exercise , 1997, Diabetes.

[23]  Jiahuai Han,et al.  The primary structure of p38 gamma: a new member of p38 group of MAP kinases. , 1996, Biochemical and biophysical research communications.

[24]  D. Moller,et al.  Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. , 1996, The American journal of physiology.

[25]  Wei Guo,et al.  Characterization of the Structure and Function of a New Mitogen-activated Protein Kinase (p38β)* , 1996, The Journal of Biological Chemistry.

[26]  L Bibbs,et al.  A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. , 1994, Science.

[27]  J. Zierath,et al.  Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose. , 1990, The American journal of physiology.

[28]  J. Zierath,et al.  Prolonged increase in insulin-stimulated glucose transport in muscle after exercise. , 1989, The American journal of physiology.

[29]  E. Richter,et al.  Effect of exercise on insulin action in human skeletal muscle. , 1989, Journal of applied physiology.

[30]  N. Ruderman,et al.  Enhanced muscle glucose metabolism after exercise: modulation by local factors. , 1984, The American journal of physiology.

[31]  E. Ravussin,et al.  Effect of muscle glycogen depletion on in vivo insulin action in man. , 1983, The Journal of clinical investigation.

[32]  N. Ruderman,et al.  Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. , 1982, The Journal of clinical investigation.

[33]  R. Somwar,et al.  Activation of p 38 Mitogen-Activated Protein Kinase and by Insulin and Contraction in Rat Skeletal Muscle Potential Role in the Stimulation of Glucose Transport , 2000 .