Effect of exogenous gamma-aminobutyric acid (GABA) on hepatic insulin-like growth factor I (IGF-I) and IGF-I binding protein (IGFBP-I) mRNA abundance following partial hepatectomy in rats.

Abstract

Insulin-like growth factor I (IGF-I) and IGF-I binding protein (IGFBP-I) are highly expressed in the liver and may play an important role in enhancing hepatic regeneration following partial hepatectomy in rats. Since hepatic levels of these growth factors are influenced by pituitary growth hormone release, which in turn is regulated by systemic serum gamma-aminobutyric acid (GABA) concentrations, we chose to examine the effects of elevated serum GABA concentrations on hepatic IGF-I and IGFBP-I mRNA abundance following partial hepatectomy in the rat. The results of our experiments revealed that at serum GABA concentrations similar to those associated with liver failure, peak hepatic IGF-I and IGFBP-I mRNA levels were significantly lower in GABA-treated rats compared with saline-treated controls (p < 0.05 and 0.01, respectively). To exclude a direct effect of GABA on hepatocyte IGF-I and IGFBP-I mRNA expression, suspensions of isolated hepatocytes were incubated in the presence and absence of exogenous GABA. In these experiments GABA treatment did not lower either IGF-I or IGFBP-I mRNA or protein levels. These findings suggest that increased concentrations of GABA in the systemic circulation could contribute to the impairment in hepatic regenerative activity that occurs in animals and humans with advanced liver failure.