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Am J Physiol Gastrointest Liver Physiol 291: G744-G750, 2006. First published June 15, 2006; doi:10.1152/ajpgi.00551.2005
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HORMONES AND SIGNALING

EGF-induced inhibition of glucose transport is mediated by PKC and MAPK signal pathways in primary cultured chicken hepatocytes

Min Young Lee,1 Soo Hyun Park,1 Yun Jung Lee,1 Jung Sun Heo,1 Jang Hern Lee,2 and Ho Jae Han1

1Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju; and 2College of Veterinary Medicine, Seoul National University, Seoul, Korea

Submitted 6 December 2005 ; accepted in final form 27 March 2006

EGF is a regulator of a wide variety of processes in various cell systems. Hepatocytes are important sites in the body's metabolism and function. Glucose transporter 2 (GLUT2) is a major transporter that is expressed strongly in hepatocytes. Therefore, this study examined the effect of EGF on GLUT2 and its related signal cascades in primary cultured chicken hepatocytes. EGF decreased [3H]deoxyglucose uptake in a dose- and time-dependent manner (>10 ng/ml, 2 h). AG-1478 (an EGF receptor antagonist) and genistein and herbimycin A (tyrosine kinase inhibitors) blocked the EGF-induced decrease in [3H]deoxyglucose uptake, which correlated with the GLUT2 expression level. In addition, the EGF-induced decrease in GLUT2 protein expression was inhibited by staurosporine, H-7, or bisindolylmaleimide I (PKC inhibitors), PD-98059 (a MEK inhibitor), SB-203580 (a p38 MAPK inhibitor), and SP-600125 (a JNK inhibitor), suggesting a role of both PKC and MAPKs (p44/42 MAPK, p38 MAPK, and JNK). In particular, EGF increased the translocation of PKC isoforms (PKC-{alpha}, -beta1, -{gamma}, -{delta}, and -{zeta}) from the cytosol to the membrane fraction and increased the activation of p44/42 MAPK, p38 MAPK, and JNK. Moreover, PKC inhibitors blocked the EGF-induced phosphorylation of three MAPKs. In conclusion, EGF decreases the GLUT2 expression level via the PKC-MAPK signal cascade in chicken hepatocytes.

epidermal growth factor; glucose transporter 2; protein kinase C; mitogen-activated protein kinases



Address for reprint requests and other correspondence: H. J. Han, Dept. of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National Univ., Gwangju 500-757, Korea (e-mail: hjhan{at}chonnam.ac.kr)




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