Effect of Ghrelin on Hepatic IGF-Binding Protein-1 Production

Moira S Lewitt

doi:10.1155/2013/751401

Abstract

Ghrelin plays key roles in energy homeostasis by central and peripheral actions that include effects on insulin signalling pathways in liver. Insulin is an important inhibitor of production by hepatocytes of insulin-like growth factor-binding protein-1 (IGFBP-1) which has an endocrine role to inhibit IGF availability. The effects of ghrelin, insulin, an AMPK activator, and an AMPK inhibitor on IGFBP-1 secretion were studied in H4-II-E rat liver cells. Ghrelin (100 nM) blocked the inhibitory effect of a maximally effective concentration of insulin (10 ng/mL) on IGFBP-1 secretion during a 5 h incubation period (P < 0.001) in the absence and presence of an AMPK inhibitor. Ghrelin, alone, had no effect on IGFBP-1 production, but enhanced secretion independently of insulin under conditions of AMPK activation (P < 0.001). In conclusion, IGFBP-1 is identified as a novel target of ghrelin action in liver that may contribute to its metabolic effects in obesity.

Highlights

Insulin-like growth factor-binding protein-1 (IGFBP-1) is a member of a family of six IGFBPs, which have effects on cell metabolism, motility, growth, and survival via IGFdependent and -independent mechanisms [1]
Ghrelin is essential for blood glucose control in starvation [13, 14]. ese metabolic effects are mediated in part by a central stimulatory effect of ghrelin on appetite and GH release and in part by peripheral actions on insulin secretion and insulin sensitivity, and hepatic glucose production [12, 15]
F 2: Ghrelin enhances the stimulatory effect of AICAR on IGFBP-1 secretion by H4-II-E cells

Summary

Introduction

Insulin-like growth factor-binding protein-1 (IGFBP-1) is a member of a family of six IGFBPs, which have effects on cell metabolism, motility, growth, and survival via IGFdependent and -independent mechanisms [1]. Circulating levels of the gut peptide ghrelin are elevated in this syndrome [7, 8], whilst they are low in simple obesity [9, 10]. Ese metabolic effects are mediated in part by a central stimulatory effect of ghrelin on appetite and GH release and in part by peripheral actions on insulin secretion and insulin sensitivity, and hepatic glucose production [12, 15]. We have previously used the insulin-sensitive rat hepatoma cell line H4-II-E to explore the factors regulating IGFBP-1 production. Stimulating AMP-activated protein kinase (AMPK) increases hepatic IGFBP-1 secretion and attenuates the inhibitory effect of insulin [16]. E aim of this study was to determine the short term effect of acylated ghrelin on IGFBP-1 secretion by H4-II-E cells Acylated ghrelin is reported to have a direct effect on intracellular insulin receptor signaling in this cell line [17]. e aim of this study was to determine the short term effect of acylated ghrelin on IGFBP-1 secretion by H4-II-E cells

Methods

Results

Discussion

Conclusion