Islet loss and alpha cell expansion in type 1 diabetes induced by multiplelow-dose streptozotocin administration in mice

The aim of this study was to investigate the alpha cell population during t he development of type 1 diabetes following multiple low-dose streptozotoci n administration in mice. For this purpose C57BL/Ks male mice were injected with streptozotocin (40 mg/kg body weight for 5 days). Development of hype rglycemia was monitored over 28 days and a morphometric analysis of islet e ndocrine cells was performed. A reduction of islet cell area was observed a fter two injections of streptozotocin. The subsequent decrease of the area throughout the study period averaged 35%. Insulin-positive beta cells gradu ally disappeared from the identified islets. Hyperglycemia was present from day 7 onwards and in parallel with hyper-glycemia, insulitis developed. An analysis of the alpha cell number per islet area revealed a 2- to 3-fold i ncrease in this cell population, with the highest value on day 21. Confocal microscopy analysis of the ICA 512 protein tyrosine phosphatase revealed s trong expression in the alpha cells at day 21, suggesting high secretory ac tivity in the diabetic state. It is concluded that multiple low-dose strept ozotocin treatment of C57BL/Ks male mice causes the disappearance of a frac tion of the islets of Langerhans. In the remaining islet tissue an expansio n of alpha cells occurs, reflecting a loss of intraislet beta cells as well as a regeneration of alpha cells.