Impaired beta-cell regeneration in perinatally malnourished rats: a study with STZ

We investigated the mechanisms implicated in beta -cell mass reduction obse rved during late fetal and early postnatal malnutrition in the rat. Beta-ce ll regeneration, including proliferation and neogenesis, was studied after neonatal beta -cell destruction by streptozotocin (STZ). STZ was injected a t birth and maternal food restriction was continued until weaning. Beta-cel l mass, proliferation, and islet number were quantified by morphometrical m easurements on pancreatic sections in STZ-injected normal (C-STZ) and malno urished (R-STZ) rats, with noninjected C and R rats as controls. At day 4, only 20% of the beta cell-mass remained in C-STZ rats. It regenerated to 50 % that of noninjected controls, mainly through active neogenesis, as shown by the entire recovery of islet number/cm(2), and also through moderately i ncreased beta -cell proliferation. In contrast, beta -cell mass from R-STZ animals poorly regenerated, despite a dramatic increase of beta -cell proli feration, because islet number/cm(2) recovered insufficiently. In conclusio n, perinatal malnutrition impairs neogenesis and the capacity of beta -cell regeneration by neogenesis but preserves beta -cell proliferation, which r emains the elective choice to increase beta -cell mass. These results provi de an explanation for the impaired capacity of malnourished animals to adap t their beta -cell mass during aging or pregnancy, which aggravate glucose tolerance.