Home
  >  
Section 11
  >  
Chapter 10,382

Contraction inhibits insulin-stimulated insulin receptor substrate-1/2-associated phosphoinositide 3-kinase activity, but not protein kinase B activation or glucose uptake, in rat muscle

Whitehead, J.P.; Soos, M.A.; Aslesen, R.; O'rahilly, S.; Jensen, J.

Biochemical Journal 349 Pt 3: 775-781

2000

ISSN/ISBN: 0264-6021
PMID: 10903138
DOI: 10.1042/bj3490775
Accession: 010381186
Download citation:  
Text
  |  
BibTeX
  |  
RIS
The initial stages of insulin-stimulated glucose uptake are thought to involve tyrosine phosphorylation of insulin receptor substrates (IRSs), which recruit and activate phosphoinositide 3-kinase (PI 3-kinase), leading to the activation of protein kinase B (PKB) and other downstream effectors. In contrast, contraction stimulates glucose uptake via a PI 3-kinase-independent mechanism. The combined effects of insulin and contraction on glucose uptake are additive. However, it has been reported that contraction causes a decrease in insulin-stimulated IRS-1-associated PI 3-kinase activity. To investigate this paradox, we have examined the effects of contraction on insulin-stimulated glucose uptake and proximal insulin-signalling events in isolated rat epitrochlearis muscle. Stimulation by insulin or contraction produced a 3-fold increase in glucose uptake, with the effects of simultaneous treatment by insulin and contraction being additive. Wortmannin completely blocked the additive effect of insulin in contracting skeletal muscle, indicating that this is a PI 3-kinase-dependent effect. Insulin-stimulated recruitment of PI 3-kinase to IRS-1 was unaffected by contraction; however, insulin produced no discernible increase in PI 3-kinase activity in IRS-1 or IRS-2 immunocomplexes in contracting skeletal muscle. Consistent with this, contraction inhibited insulin-stimulated p70(S6K) activation. In contrast, insulin-stimulated activation of PKB was unaffected by contraction. Thus, in contracting skeletal muscle, insulin stimulates glucose uptake and activates PKB, but not p70(S6K), by a PI 3-kinase-dependent mechanism that is independent of changes in IRS-1- and IRS-2-associated PI 3-kinase activity.

PDF emailed within 0-6 h: $19.90




Related References

Venable, C.L.; Frevert, E.U.; Kim, Y.B.; Fischer, B.M.; Kamatkar, S.; Neel, B.G.; Kahn, B.B. 2000: Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation Journal of Biological Chemistry 275(24): 18318-18326
Chin, J.E.; Feng, L.I.U.; Roth, R.A. 1994: Activation of protein kinase Cα inhibits insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 Molecular Endocrinology (Baltimore, Md.) 8(1): 51-58
Chin, J.E.; Liu, F.; Roth, R.A. 1994: Activation of protein kinase C alpha inhibits insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 Molecular Endocrinology 8(1): 51-58
Walaas, O.; Horn, R.S.; Walaas, S.I. 1997: The protein kinase C pseudosubstrate peptide (PKC19-36) inhibits insulin-stimulated protein kinase activity and insulin-mediated translocation of the glucose transporter glut 4 in streptolysin-O permeabilized adipocytes FEBS Letters 413(1): 152-156
Gomes, D.M., D.S.; Ouwens, D.M.; Maassen, J.A. 1999: Hyperosmolarity activates the insulin receptor tyrosine kinase, but inhibits insulin-stimulated glucose uptake Diabetes 48(Suppl 1): A333
Bandyopadhyay, G.; Standaert, M.L.; Sajan, M.P.; Karnitz, L.M.; Cong, L.; Quon, M.J.; Farese, R.V. 1999: Dependence of insulin-stimulated glucose transporter 4 translocation on 3-phosphoinositide-dependent protein kinase-1 and its target threonine-410 in the activation loop of protein kinase C-zeta Molecular Endocrinology 13(10): 1766-1772
Chappell, D.S.; Patel, N.A.; Jiang, K.; Li, P.; Watson, J.E.; Byers, D.M.; Cooper, D.R. 2009: Functional involvement of protein kinase C-βII and its substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), in insulin-stimulated glucose transport in L6 rat skeletal muscle cells Diabetologia (Berlin) 52(5): 901-911
Vollenweider, P.; Menard, B.; Nicod, P. 2002: Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (ζ/λ) activation in myotubes from obese patients with impaired glucose tolerance Diabetes (New York) 51(4): 1052-1059
Vollenweider, P.; Ménard, B.; Nicod, P. 2002: Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (zeta/lambda) activation in myotubes from obese patients with impaired glucose tolerance Diabetes 51(4): 1052-1059
Chappell, D.S.; Patel, N.A.; Jiang, K.; Li, P.; Watson, J.E.; Byers, D.M.; Cooper, D.R. 2009: Functional involvement of protein kinase C-betaIi and its substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), in insulin-stimulated glucose transport in L6 rat skeletal muscle cells Diabetologia 52(5): 901-911
Harada, S.; Smith, R.M.; Smith, J.A.; White, M.F.; Jarett, L. 1996: Insulin-induced egr-1 and c-fos expression in 32D cells requires insulin receptor, Shc, and mitogen-activated protein kinase, but not insulin receptor substrate-1 and phosphatidylinositol 3-kinase activation Journal of Biological Chemistry 271(47): 30222-30226
Su, X.; Lodhi, I.J.; Saltiel, A.R.; Stahl, P.D. 2006: Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5 Journal of Biological Chemistry 281(38): 27982-27990
Su, X.; Lodhi, I.J.; Saltiel, A.R. 2006: Insulin-stimulated Interaction between Insulin Receptor Substrate 1 and p85a and Activation of Protein Kinase B/Akt Require Rab5 Journal of Biological Chemistry 281(38): 982-990
Temofonte, N.; Sajan, M.P.; Nimal, S.; Pastoor, T.; Fumero, C.; Casaubon, L.; Powe, J.L.; Standaert, M.L.; Farese, R.V. 2009: Combined thiazolidinedione-metformin treatment synergistically improves insulin signalling to insulin receptor substrate-1-dependent phosphatidylinositol 3-kinase, atypical protein kinase C and protein kinase B/Akt in human diabetic muscle Diabetologia 52(1): 60-64
Pirola, L.; Bonnafous, S.; Johnston, A.M.; Chaussade, C.; Portis, F.; Van Obberghen, E. 2003: Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells Journal of Biological Chemistry 278(18): 15641-15651
Shih, K.C.; Kwok, C.F.; Ho, L.T. 2000: Combined use of insulin and endothelin-1 causes decrease of protein expression of beta-subunit of insulin receptor, insulin receptor substrate-1, and insulin-stimulated glucose uptake in rat adipocytes Journal of Cellular Biochemistry 78(2): 231-240
Takenaka, N.; Araki, N.; Satoh, T. 2019: Involvement of the protein kinase Akt2 in insulin-stimulated Rac1 activation leading to glucose uptake in mouse skeletal muscle Plos one 14(2): E0212219
Howlett, K.F.; Sakamoto, K.; Yu, H.; Goodyear, L.J.; Hargreaves, M. 2006: Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise Metabolism, Clinical and Experimental 55(8): 1046-1052
Wick, K.R.; Werner, E.D.; Langlais, P.; Ramos, F.J.; Dong, L.Q.; Shoelson, S.E.; Liu, F. 2002: Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor Journal of Biological Chemistry 278(10): 8460-8467
Montagnani, M.; Ravichandran, L.V.; Chen, H.; Esposito, D.L.; Quon, M.J. 2002: Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells Molecular Endocrinology 16(8): 1931-1942