epidermal-growth-factor and Pancreatic-Diseases

This article is aimed at reviewing and analyzing studies that are related to the possible therapeutic use of a potent and ubiquitously-distributed hormone--somato-statin (SS-14), and its analogues. Administration of these substances has provided beneficial effects in treating acromegaly, gastro-intestinal hemorrhagic and hypersecretory disorders, acute pancreatitis, diabetes mellitus, and certain types of cancer. Further studies with SS-14-analogues might provide new therapies for treating certain life-threatening disorders of man.

Topics: Acromegaly; Alzheimer Disease; Epidermal Growth Factor; Gastrointestinal Diseases; Humans; Neoplasms; Pancreatic Diseases; Somatostatin

Topics: Animals; Cattle; Cholecystokinin; Dogs; Enteral Nutrition; Epidermal Growth Factor; Gastrins; Hormones; Humans; Insulin; Intestine, Small; Pancreas; Pancreatic Diseases; Pancreatic Polypeptide; Parasympathomimetics; Pituitary Gland; Rats; Secretin; Trypsin Inhibitors

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is expressed in both normal pancreatic islets and in pancreatic cancers, but its role in pancreatic physiology and disease is not known. This report examines the effects of HB-EGF overexpression in mouse pancreas.. Transgenic mice were established using a tissue-specific promoter to express an HB-EGF complementary DNA in pancreatic beta cells, effectively elevating HB-EGF protein 3-fold over endogenous levels.. Mice overexpressing HB-EGF in pancreatic islets showed both endocrine and exocrine pancreatic defects. Initially, islets from transgenic mice failed to segregate alpha, beta, delta, and PP cells appropriately within islets, and had impaired separation from ducts and acini. Increased stroma was detected within transgenic islets, expanding with age to cause fibrosis of both endocrine and exocrine compartments. In addition to these structural abnormalities, subsets of transgenic mice developed profound hyperglycemia and/or proliferation of metaplastic ductal epithelium. Both conditions were associated with severe stromal expansion, suggesting a role for islet/stromal interaction in the onset of the pancreatic disease initiated by HB-EGF. Supporting this conclusion, primary mouse fibroblasts adhered to transgenic islets when the 2 tissues were cocultured in vitro, but did not interact with nontransgenic islets.. An elevation in HB-EGF protein in pancreatic islets led to altered interactions among islet cells and among islets, stromal tissues, and ductal epithelium. Many of the observed phenotypes appeared to involve altered cell adhesion. These data support a role for islet factors in the development of both endocrine and exocrine disease.

Topics: Animals; Cell Communication; Cell Division; Epidermal Growth Factor; Epithelial Cells; Fibroblasts; Fibrosis; Gene Expression; Heparin-binding EGF-like Growth Factor; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Metaplasia; Mice; Mice, Transgenic; Pancreatic Diseases; Pancreatic Ducts; Phenotype