INDUCTION OF ISLET-CELL DIFFERENTIATION AND NEW ISLET FORMATION IN THE HAMSTER - FURTHER SUPPORT FOR A DUCTULAR ORIGIN

Partial obstruction of the adult hamster pancreas leads to islet cell differentiation and new islet formation. From morphologic and morphome tric observations, we have tentatively identified the source of the ne w islet tissue to be from cells in the ducts. In this study, in vivo l abeling with a single pulse of tritiated thymidine after partial duct obstruction was used to ascertain whether newly formed islet cells wer e in fact derived from cells in the ductal epithelium. Supportive evid ence for this formulation was also sought using immunocytochemistry fo r islet hormones and in situ hybridization for glucagon and insulin mR NA to probe areas of proliferating duct cells. Endocrine cell differen tiation was observed as a migration of cells out from small ducts begi nning at about 10 days after obstruction. Duct and islet cell labeling indices (LI; %) in control animals remained at a low level (0.25 +/- 0.01 and 0.26 +/- 0.03, respectively) throughout the experiment. In co ntrast, at 2 weeks after partial obstruction, the duct and islet cell LI were 4.2 +/- 0.7 and 0.80 +/- 0.1 (p < 0.05 vs. control). After 2 w eeks, there was a rapid and significant 86% decline in the duct cell L I to a low of 0.6 +/- 0.2 at 8 weeks, which was accompanied by a compa rable, but reciprocal, 113% increase in the islet cell LI to a high of 1.7 +/- 0.8 (p < 0.05). In situ hybridization demonstrated glucagon a nd insulin mRNA-positive cells within intralobular ducts as early as 6 and 8 days, respectively, after obstruction. Glucagon and insulin pep tides appeared in these cells at similar to 8 and 10 days, respectivel y, as cells migrated out from the duct wall, This study provides addit ional evidence that further supports our concept that pancreatic endoc rine cell differentiation in this model reiterates the normal ontogeny of beta cell differentiation from cells in the ductular epithelium.