To trace the ontogeny of beta cell regrowth in adult transgenic mice t
hat produce interferon-gamma in the islets (ins-IFN-gamma), their exis
ting beta cells were depleted by treatment with high doses of streptoz
otocin (STZ). Initially, beta cell necrosis and degranulation were app
arent in STZ-treated mice of both the BALB/c and the ins-IFN-gamma tra
nsgenic strains. The newly emerging transitional cells were then chara
cterized by ultra-structural analysis. Interestingly, transitional cel
ls harboring both exocrine and endocrine granules appeared frequently
in ins-IFN-gamma transgenics after high-dose STZ treatment. New beta c
ells were produced primarily by the formation of new islets from the s
mall pancreatic ducts. beta cell regeneration in the ins-IFN-gamma tra
nsgenic mouse model is thus explained primarily by the budding of new
islets from the ducts with acinar cells as possible precursors of isle
t cells.