THE ENDOCRINE SECRETION OF HUMAN INSULIN AND GROWTH-HORMONE BY EXOCRINE GLANDS OF THE GASTROINTESTINAL-TRACT

The exocrine pancreas, liver, and submandibular glands of the rat were used to express and secrete two exogenous, human protein hormones (gr owth hormone and insulin) into blood at physiological concentrations. Transfection, expression, and secretion were achieved by the in vivo r etrograde injection of plasmid DNA into the secretory ducts of these g lands. Pancreatic acinar cells secreted physiological concentrations o f growth hormone into the circulation, and its secretion was enhanced by cholinergic stimulation. A human insulin gene was engineered to all ow normal processing of insulin in non-beta cells. With this gene, the secretion of human insulin by the exocrine pancreas normalized elevat ed blood glucose levels in diabetic rats. These in vivo observations d emonstrate the utility of retrograde ductal administration of naked DN A into exocrine organs as a novel method for the regulated systemic de livery of protein-based pharmaceuticals.