Hepatocyte growth factor inhibits insulin-stimulated glycogen synthesis in primary cultured hepatocytes.
OBJECTIVE
Hepatocyte growth factor (HGF) plays an important role as a mitogen in liver regeneration. However, little is known about the metabolic effects of HGF in the liver. Studies were performed to examine whether HGF influences carbohydrate metabolism, which is drastically changed in the early course of the regeneration.


METHODS
Primary cultured rat hepatocytes were treated with glucoregulatory hormones such as insulin, glucagon and adrenaline in the presence or absence of HGF. Cellular glycogen deposition and activities of its metabolic enzymes were compared.


RESULTS
HGF inhibited insulin-stimulated glycogen deposition, but had no effect on glycogen degradation stimulated by glucagon and adrenaline. HGF decreased glycogen synthase activity and increased glycogen phosphorylase activity in insulin-stimulated hepatocytes, resulting in the inhibition of glycogen synthesis. Experiments with immunoprecipitation revealed that HGF had no effect on the upstream of insulin signaling including an activation of its receptor and association of insulin receptor substrate with phosphatidylinositol 3-kinase, indicating that HGF presumably affects further downstream of these events.


CONCLUSIONS
These results demonstrate that HGF interacts with insulin on glucose metabolism in hepatocytes. HGF may be involved in glucose regulation, and contribute to cell growth and maturation in addition to its mitogenic action during liver regeneration.
Kaibori
Masaki
M
First Department of Surgery, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8506, Japan.
Kwon
A-Hon
AH
Teshima
Shigeru
S
Nakanishi
Hideki
H
Kitano
Takahiro
T
Kamiyama
Yasuo
Y
Okumura
Tadayoshi
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D006003:Glycogen / Q000096:biosynthesis* / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007004:Hypoglycemic Agents; D007328:Insulin; D017228:Hepatocyte Growth Factor; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase