INSULIN, TRANSFORMING GROWTH-FACTORS, AND SUBSTRATES MODULATE GROWTH OF GUINEA-PIG PANCREATIC DUCT CELLS IN-VITRO

Background & Aims: Little is known of the physiological mechanisms tha t control cellular renewal in the pancreatic excretory duct system. Th is study investigated the effects of potential regulatory substances o n the growth of cultured guinea pig pancreatic duct epithelial monolay ers. Methods: Pancreatic duct explants were cultured for 3 days on pla stic and on permeable filters in the presence and absence of different substances. Growth of epithelial monolayers from these explants was m easured by 5-bromo-2'-deoxyuridine incorporation and morphometric proc edures. Results: Epidermal growth factor and insulin both enhanced mon olayer growth and together had an additive effect. Transforming growth factor alpha enhanced and transforming growth factor beta inhibited g rowth, whereas glucagon, somatostatin, pancreatic polypeptide, secreti n, cerulein, bombesin, and dexamethasone had no significant effects. M onolayer growth on type I collagen-coated filters was enhanced when co mpared with that of monolayers grown on tissue culture plastic. Cell g rowth from explants on filters coated with type IV collagen and fibron ectin was comparable with that on plastic, whereas growth on Matrigel- or laminin-coated filters was reduced. Conclusions: insulin, transfor ming growth factors, and substrate components modulate growth of pancr eatic duct epithelial cells in vitro, suggesting that they are importa nt regulators of cell division in the excretory duct system of the int act pancreas.