Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications
Glucose uptake in adipose tissue and its regulation by ghrelin. Insulin activates the IR, which phosphorylates and recruits different substrate adaptors such as the IRS family of proteins. Tyrosine phosphorylated IRS then displays binding sites for numerous signaling partners. Among them, PI3K has a major role in insulin function, mainly via the activation of the AKT/PKB and the PKCz cascades. Activated AKT induces glycogen synthesis, through inhibition of GSK-3. Insulin stimulates glucose uptake in muscle and adipocytes via translocation of GLUT-4 vesicles to the plasma membrane. GLUT-4 translocation involves the PI3K/AKT pathway. Ghrelin treatment induced increases IRS-1 and AKT phosphorylation, but when the adipocytes were treated with wortmannin, a PI3K inhibitor, completely blocked this ghrelin induced increase in glucose transport and phospho-AKT expression, suggesting that PI3K/AKT activation may mediate the effect of ghrelin on glucose transport in these adipocytes.