A longitudinal ultrastructural study of pancreatic cellular damage in murine streptozotocin diabetes

Using islets obtained by collagenase digestion, we have carried out a longitudinal study of the ultrastructure of endocrine cells of the islets of Langerhans from C57BL/6 mice, during the development of diabetes induced by the multiple low-dose streptozotocin (mld STZ) technique, with and without co-treatment with complete Freund's adjuvant (CFA). Diabetes, as assessed by glycemia, occurred on different days in the various treatment groups following the initial STZ injection. It was observed on day 7 in 4/7 and 3/7 animals treated with mld STZ and with CFA plus mld STZ respectively, on day 14 in 3/6 animals treated with CFA plus sub mld STZ and on day 21 in 2/5 animals treated with sub mld STZ. Breakages in the basement membrane of the B-cell, and severe vacuolation, occurred in all STZ treated animals, despite normoglycemia in animals in the sub-mld group. Mononuclear cells (macrophages acutely and lymphocytes chronically) were observed in islets from animals with mld STZ irrespective of treatment with CFA, but were found adjacent to acinar cells only in those animals treated with CFA. Damage to acinar cells was observed exclusively in this group. In sub mld STZ treated animals, mononuclear cells were found only in those animals treated with CFA. These findings are discussed with reference to the etiopathology of the disease.