CLONING AND SEQUENCING OF THE PANCREATIC-ISLET NEOGENESIS ASSOCIATED PROTEIN (INGAP) GENE AND ITS EXPRESSION IN ISLET NEOGENESIS IN HAMSTERS

Induction of islet neogenesis by cellophane wrapping (CW) reverses str eptozotocin-induced (STZ) diabetes, Administration of Ilotropin, a pro tein extract isolated from CW pancreata, causes recapitulation of norm al islet ontogeny and reverses STZ diabetes, reducing mortality by 50% . We investigated the hypothesis that a novel gene encoding a constitu ent of Ilotropin was expressed in the hamster pancreas undergoing isle t neogenesis, Islet neogenesis associated protein (INGAP) is a product of a novel gene expressed in regenerating hamster pancreas. Northern blot analysis showed a strong single transcript of 850 bp at 1 and 2 d after CW that disappeared by the 6th day and was absent from untreate d control pancreata, INGAP gene is expressed in acinar cells, but not in islets, Western blot analysis demonstrated the presence of INGAP in Ilotropin but not in extracts from control pancreata, A synthetic pen tadecapeptide. corresponding to a region unique to INGAP, stimulated a 2.4-fold increase in [H-3]thymidine incorporation into hamster duct e pithelium in primary culture and a rat pancreatic duct cell line but h ad no effect on a hamster insulinoma tumor cell line, A portion of hum an INGAP gene was cloned and appears to be highly homologous to the ha mster gene, This data suggests that the INGAP gene is a novel pancreat ic gene expressed during islet neogenesis whose protein product is a c onstituent of Ilotropin and is capable of initiating duct cell prolife ration, a prerequisite for islet neogenesis.