Frontiers of pancreas regeneration.

Recent advances in molecular biological techniques have made the search for the factors in pancreas regeneration more intensive. Many transcription factors and growth factors have been suggested to be involved in the proliferation, differentiation, and maintenance of endocrine and exocrine pancreas. Among the transcription factors, PDX-1 has been examined in a major pancreatectomy model and is suggested to play a role in beta-cell differentiation. Among the growth factors and related peptides, reg protein seems to be a promising candidate which can be applied to clinical practice. Our previous study showed that proton pump inhibitor-induced endogenous hypergastrinemia enhanced insulin secretion and pancreas regeneration. Our results and other studies have suggested that endogenous gastrin induces beta-cell differentiation. On the other hand, the role of classical gut hormones such as gastrin and cholecystokinin in pancreas regeneration has become less significant, as it has been shown that rodents deficient in the genes for these hormones form almost normal pancreas. Results in dogs have shown that pancreas regeneration occurs after major pancreatectomy. A preliminary experiment in primates also suggests latent developmental capacity in the adult primate pancreas. These results lead us to expect that regeneration of the remnant pancreas after subtotal pancreatectomy would be a good target of certain therapies to enhance pancreatic regeneration.