ISLET PATHOLOGY IN STREPTOZOTOCIN-INDUCED AUTOIMMUNE DIABETIC MICE - NEW INSIGHTS INTO CLINICAL-PRACTICE

The pathogenesis of spontaneous remission in Type 1 diabetes is poorly understood. To clarify this particu lar 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 fit-st 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 occulted on the first or second day after STZ injection. Sustained hyperglycaemia, hypo-insulinaemia and islet cell antibody positivi ty 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 inflammed islets were filled with insulin and a cells appeared to be hyperplastic in the diabetic group. Our experimental findings an in accordance with clinical practice in Type diabetes mellitus; namely, the improval of metabolic as well as immunological parameters indicates that the diseased islets which are demonstrated to be filled with insulin have regained their endogenous insulin production and release capacity during the remission period. In conclusion, this study shows that different stages of immune attacks occur In the same pancreas; in lymph nodes lymphocytes transform into plasma cells as evidenced by autoantibody positivity and finally, the beta cells in inflamed (insulitis) Islets remain filled with insulin at the acute hyperglycaemic, hypoinsulinaemic and ketoacidstic phase of Type 1 diabetes mellitus.