PMID- 16159907 OWN - NLM STAT- MEDLINE DCOM- 20060227 LR - 20161124 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 290 IP - 1 DP - 2006 Jan TI - Are tyrosine kinases involved in mediating contraction-stimulated muscle glucose transport? PG - E123-E128 AB - Muscle contractions and insulin stimulate glucose transport into muscle by separate pathways. The contraction-mediated increase in glucose transport is mediated by two mechanisms, one involves the activation of 5'-AMP-activated protein kinase (AMPK) and the other involves the activation of calcium/calmodulin-dependent protein kinase II (CAMKII). The steps leading from the activation of AMPK and CAMKII to the translocation of GLUT4 to the cell surface have not been identified. Studies with the use of the tyrosine kinase inhibitor genistein suggest that one or more tyrosine kinases could be involved in contraction-stimulated glucose transport. The purpose of the present study was to determine the involvement of tyrosine kinases in contraction-stimulated glucose transport in rat soleus and epitrochlearis muscles. Contraction-stimulated glucose transport was completely prevented by pretreatment with genistein (100 microM) and the related compound butein (100 microM). However, the structurally distinct tyrosine kinase inhibitors 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyridine and herbimycin did not reduce contraction-stimulated glucose transport. Furthermore, genistein and butein inhibited glucose transport even when muscles were exposed to these compounds after being stimulated to contract. Muscle contractions did not result in increases in tyrosine phosphorylation of proteins such as proline-rich tyrosine kinase and SRC. These results provide evidence that tyrosine kinases do not mediate contraction-stimulated glucose transport and that the inhibitory effects of genistein on glucose transport result from direct inhibition of the glucose transporters at the cell surface. FAU - Wright, David C AU - Wright DC AD - Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. FAU - Geiger, Paige C AU - Geiger PC FAU - Han, Dong-Ho AU - Han DH FAU - Holloszy, John O AU - Holloszy JO LA - eng GR - AG-00078/AG/NIA NIH HHS/United States GR - DK-18986/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20050913 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (AG 1879) RN - 0 (Benzoquinones) RN - 0 (Chalcones) RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (Lactams, Macrocyclic) RN - 0 (Pyrimidines) RN - 0 (Quinones) RN - 1W306TDA6S (Rifabutin) RN - 4WVS5M0LGF (butein) RN - 5S5A2Q39HX (Chalcone) RN - 70563-58-5 (herbimycin) RN - 9G2MP84A8W (Deoxyglucose) RN - DH2M523P0H (Genistein) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Focal Adhesion Kinase 2) RN - EC 2.7.10.2 (src-Family Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Benzoquinones MH - Biological Transport/drug effects MH - Chalcone/analogs & derivatives/pharmacology MH - Chalcones MH - Deoxyglucose/pharmacokinetics MH - Electric Stimulation MH - Focal Adhesion Kinase 2/antagonists & inhibitors/metabolism MH - Genistein/pharmacology MH - Glucose/*pharmacokinetics MH - Glucose Transporter Type 4/metabolism MH - Hypoxia/physiopathology MH - In Vitro Techniques MH - Insulin/pharmacology MH - Lactams, Macrocyclic MH - Male MH - Muscle Contraction/*physiology MH - Muscle, Skeletal/drug effects/metabolism/*physiology MH - Phosphorylation/drug effects MH - Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism MH - Pyrimidines/pharmacology MH - Quinones/pharmacology MH - Rats MH - Rats, Wistar MH - Rifabutin/analogs & derivatives MH - src-Family Kinases/antagonists & inhibitors/metabolism EDAT- 2005/09/15 09:00 MHDA- 2006/02/28 09:00 CRDT- 2005/09/15 09:00 PHST- 2005/09/15 09:00 [pubmed] PHST- 2006/02/28 09:00 [medline] PHST- 2005/09/15 09:00 [entrez] AID - 00280.2005 [pii] AID - 10.1152/ajpendo.00280.2005 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E123-E128. doi: 10.1152/ajpendo.00280.2005. Epub 2005 Sep 13.