Effect of growth hormone on the translocation of GLUT4 and its relation to insulin-like and anti-insulin action.
To elucidate the effect of growth hormone (GH) on the insulin signal transduction pathway leading to the translocation of glucose transporter-4 (GLUT4), we constructed Chinese hamster ovary cells that overexpressed GH receptor and GLUT4. Treatment with GH triggered GLUT4 translocation, and this translocation was completely inhibited by wortmannin. GH-induced GLUT4 translocation reached a maximum level after 30 min, and then gradually decreased and returned to the basal level after 2 h. Tyrosine phosphorylation of JAK2 also became maximal after 30 min and then gradually decreased. In contrast, GLUT4 translocation remained unchanged for 2 h after insulin treatment, and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) also remained constant for up to 2 h. Chronic GH treatment had almost no effect on insulin-stimulated Akt kinase activation and GLUT4 translocation. These results suggest that GH and insulin translocate GLUT4 in a similar manner, at least in part, and the difference in translocation depends on the difference in the tyrosine phosphorylation of JAK2 and IRS-1. The anti-insulin action of GH after chronic GH treatment does not appear to be mainly due to the inhibition of GLUT4 translocation.
Yokota
I
I
Department of Pediatrics, School of Medicine, University of Tokushima, 3-Kuramoto cho, Tokushima City, Tokushima 770, Japan. yichiro@clin.med.tokushima-u.ac.jp
Hayashi
H
H
Matsuda
J
J
Saijo
T
T
Naito
E
E
Ito
M
M
Ebina
Y
Y
Kuroda
Y
Y
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D051275:Glucose Transporter Type 4; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D000077191:Wortmannin