Insulin suppresses hepatitis B surface antigen expression in human hepatoma cells.
The human hepatoma Hep3B cells contain integrated hepatitis B viral genome and continually secret hepatitis B surface antigen (HBsAg). The production of HBsAg (but not alpha-fetoprotein) was suppressed by addition of low concentrations (0.1-1 nM) of insulin into serum-free medium. In addition, the suppression of HBsAg production by insulin was paralleled with the decrease in HBsAg mRNA abundance. Insulin also cause a rapid rate of disappearance of HBsAg mRNA (t 1/2, 2 h) in Hep3B cells. The Hep3B cells carry specific receptor with high affinity for insulin (Kd = 1.8 nM). The receptor showed an insulin-dependent protein tyrosine kinase activity. The half-maximal insulin concentration for the activation of the receptor kinase was about 5 nM. Only very high concentrations of insulin-like growth factor I and human proinsulin can compete for the insulin receptor binding and suppress HBsAg production, this suggests that insulin may act through its receptor binding to suppress HBsAg expression in human hepatoma Hep3B cells.
Chou
C K
CK
Department of Medical Research, Veterans General Hospital, Taipei, Taiwan, Republic of China.
Su
T S
TS
Chang
C M
CM
Hu
C P
CP
Huang
M Y
MY
Suen
C S
CS
Chou
N W
NW
Ting
L P
LP
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000382:microbiology*; D002460:Cell Line; D005796:Genes / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms / Q000235:genetics / Q000382:microbiology*; D010766:Phosphorylation; D011384:Proinsulin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011972:Receptor, Insulin / Q000378:metabolism; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D000509:alpha-Fetoproteins / Q000235:genetics
D006514:Hepatitis B Surface Antigens; D007328:Insulin; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D007334:Insulin-Like Growth Factor I; D011384:Proinsulin; D011972:Receptor, Insulin