Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications
Regulation of hepatic gluconeogenesis and glycogen synthesis by ghrelin. Insulin activates the insulin receptor tyrosine kinase (IR), which phosphorylates and recruits different substrate adaptors. AKT is a key protein kinase downstream of the insulin receptor and its activation plays a key role in suppressing hepatic gluconeogenesis, since GSK-3, which phosphorylate glycogen synthetase (GS) is inhibiting, is phosphorylated by AKT suppressing hepatic gluconeogenesis, resulting in enhanced glycogen deposition. Sustained ghrelin administration in rats reduced hepatic AKT-GSK activation and enhanced PGC-1a expression, suggesting upregulation of gluconeogenesis and downregulation of glyconeogenesis.