The aim of this study was to investigate the alpha cell
population during the development of type 1 diabetes
following multiple low-dose streptozotocin administration
in mice. For this purpose C57BL/Ks male mice were
injected with streptozotocin (40 mg/kg body weight for
5 days). Development of hyperglycemia was monitored
over 28 days and a morphometric analysis of islet endocrine
cells was performed. A reduction of islet cell area was
observed after two injections of streptozotocin. The subsequent
decrease of the area throughout the study period
averaged 35%. Insulin-positive beta cells gradually disappeared
from the identified islets. Hyperglycemia was
present from day 7 onwards and in parallel with hyperglycemia,
insulitis developed. An analysis of the alpha cell
number per islet area revealed a 2- to 3-fold increase in
this cell population, with the highest value on day 21.
Confocal microscopy analysis of the ICA 512 protein
tyrosine phosphatase revealed strong expression in the
alpha cells at day 21, suggesting high secretory activity in
the diabetic state. It is concluded that multiple low-dose
streptozotocin treatment of C57BL/Ks male mice causes
the disappearance of a fraction of the islets of Langerhans.
In the remaining islet tissue an expansion of alpha cells
occurs, reflecting a loss of intraislet beta cells as well as a
regeneration of alpha cells.