Are tyrosine kinases involved in mediating contraction-stimulated muscle glucose transport?
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.
Wright
David C
DC
Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Geiger
Paige C
PC
Han
Dong-Ho
DH
Holloszy
John O
JO
D000818:Animals; D016227:Benzoquinones; D001692:Biological Transport / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004558:Electric Stimulation; D051418:Focal Adhesion Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D005947:Glucose / Q000493:pharmacokinetics*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017828:Rifabutin / Q000031:analogs & derivatives; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C412373:AG 1879; D016227:Benzoquinones; D047188:Chalcones; D051275:Glucose Transporter Type 4; D007328:Insulin; D047029:Lactams, Macrocyclic; D011743:Pyrimidines; D011809:Quinones; D017828:Rifabutin; C040918:butein; D002599:Chalcone; C020754:herbimycin; D003847:Deoxyglucose; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D005947:Glucose