Effects of betaine on ethanol-stimulated secretion of IGF-I and IGFBP-1 in rat primary hepatocytes: involvement of p42/44 MAPK activation.
OBJECTIVE
To evaluate the effects of betaine on the ethanol-induced secretion of IGF-I and IGFBP-1 using radioimmunoassay and Western blotting, respectively, in primary cultured rat hepatocytes.


METHODS
Hepatocytes isolated from male Sprague-Dawley rats were incubated with various concentrations of ethanol and PD98059 procedures. The hepatocytes were also treated with different doses of betaine (10(-5), 10(-4), and 10(-3) mol/L). We measured IGF-I and IGFBP-1 using radioimmunoassay and Western blotting, respectively.


RESULTS
The ethanol-induced inhibition of IGF-I secretion was attenuated by betaine in a concentration-dependent manner in primary cultured rat hepatocytes. At 10(-3) mol/L, betaine significantly increased IGF-I secretion but decreased IGFBP-1 secretion. In addition, p42/44 mitogen-activated protein kinase (MAPK) activity was accelerated significantly from 10 min to 5 h after treatment with 10(-3) mol/L betaine. Furthermore, the changes in IGF-1 and IGFBP-1 secretion resulting from the increased betaine-induced p42/44 MAPK activity in primary cultured rat hepatocytes was blocked by treatment with the MAPK inhibitor PD98059. Betaine treatment blocked the ethanol-induced inhibition of IGF-I secretion and p42/44 MAPK activity, and the ethanol-induced increase in IGFBP-1 secretion.


CONCLUSIONS
Betaine modulates the secretion of IGF-I and IGFBP-1 via the activation of p42/44 MAPK in primary cultured rat hepatocytes. Betaine also alters the MAPK activations induced by ethanol.
Lee
Myeong Soo
MS
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, Exeter EX2 4NT, United Kingdom.
Kim
Myung-Sunny
MS
Park
Soo Young
SY
Kang
Chang-Won
CW
D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000502:physiology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D005419:Flavonoids; D018970:Insulin-Like Growth Factor Binding Protein 1; D000431:Ethanol; D001622:Betaine; D007334:Insulin-Like Growth Factor I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one