Islet pathology in streptozotocin-induced auto-immune diabetic mice: new insights into clinical practice

The pathogenesis of spontaneous remission in Type 1 diabetes is poorly understood. To clarify this particular phase of the disease, experimental autoimmune diabetes induced by multiple low doses of streptozotocin (M-STZ) in mice was used as an experimental tool. Balb/C mice received five doses of 40 mg of STZ (diabetic group) or citrate buffer (controls) during five consecutive days. Heparinized blood samples were collected from these animals' orbital sinus in the morning following 8-12 h of fasting, before and at the 7th, 14th and 21st day after the first injection of STZ. Plasma glucose, insulin and islet cell antibodies (ICA) were determined. The animals were killed at the 21st day; their pancreata and abdominal lymph nodes were removed for morphometric and immunocytochemical examinations. Induction of hyperglycaemia occurred on the first or second day after STZ injection. Sustained hyperglycaemia, hypo-insulinaemia and islet cell antibody positivity were observed in diabetic animals. Morphometric analysis of the pancreata reveals a spectrum of mild to extensive mononuclear cell infiltration and varying degrees of beta cell destruction. In the same diabetic pancreas, morphometric analysis of islets' sections reveals a normal appearance in 42% and varying degrees of insulitis in 58%; ductulitis in 20% and islets' necrosis in 48%, indicating that many immune assaults take place simultaneously and subsequently. Furthermore, plasmocytic transformation in diabetic lymph nodes was observed, disclosing the appearance of ICA's positivity. Concerning immunocytochemical findings, alpha, beta and delta cells were normal in appearance in controls; while beta cells of inflamed islets were filled with insulin and alpha cells appeared to be hyperplastic in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)