ABSTRACT
Studies performed in vivo using genetically modified mouse models have shown that growth factors are regulators of beta-cell growth and differentiation. Hepatocyte growth factor (HGF), initially identified as a circulating factor implicated in hepatic regeneration, displays pleiotropic actions in many different tissues. In this chapter, we review the studies describing the effects of HGF in the pancreatic beta cell and beta-cell progenitors. The physiological role of HGF in the pancreatic beta cell has been recendy examined in conditional knockout mice in which HGF/c-Met signaling was disrupted in beta cells. These mice display impaired glucose-stimulated insulin secretion without significant alterations in beta-cell mass suggesting that HGF is important for controlling normal insulin secretion but dispensable for normal beta-cell growth. On the other hand, HGF administration or overexpression in beta cells has been shown to increase beta-cell proliferation, survival and differentiation, in vivo and in vitro. Based on these observations, HGF has been tested for improving islet transplantation. Interestingly, HGF gene transfer to islets ex vivo enhances islet graft survival and function and reduces the number of islets needed for successful trans plantation suggesting a potential therapeutic future for HGF in islet transplantation in hu mans. Understanding the intracellular mechanisms regulated by HGF in the beta cell that are essential for the reported beneficial effects will enormously increase the potential of HGF as a therapeutic agent for the treatment of diabetes.
