Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies

Lab Invest. 1978 Apr;38(4):470-86.


Pancreatic insulitis and diabetes mellitus were induced in Charles River CD-1 mice with five subdiabetogenic injections of streptozotocin. Plasma glucose and immunoreactive insulin levels were measured and animals were sacrificed at intervals for morphologic studies of pancreatic islets and measurements of extractable pancreatic immunoreactive insulin. Light microscopy revealed striking insulitis, 5 to 6 days after streptozotocin injections, with cell necrosis and eventual islet atrophy due to beta-cell necrosis, and numerous type C viruses within many of the surviving beta-cells. Light microscopic immunoperoxidase stains of islet cell hormones and electron microscopy identified relatively increased numbers of alpha- and delta-cells within the atrophic islets 6 and 12 months after streptozotocin injections. Plasma glucose, plasma immunoreactive insulin, and extractable pancreatic immunoreactive insulin measurements documented the persistence of profound hyperglycemia, as well as the reduction of plasma and pancreatic immunoreactive insulin levels. Immunofluorescence studies demonstrated the absence of circulating islet cell antibodies during both the acute and chronic stages of the syndrome. The pathogenesis of this model of insulin-deficient diabetes is believed to be a cell-mediated autoimmune reaction directed against pancreatic beta-cells altered by subdiabetogenic injections of streptozotocin. The importance of the increased number of type C viruses within surviving beta-cells remains obscure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Immunoglobulin G / analysis
  • Inflammation
  • Insulin / analysis
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / ultrastructure
  • Lymphocytes / ultrastructure
  • Macrophages / ultrastructure
  • Male
  • Mice
  • Retroviridae / analysis
  • Streptozocin


  • Blood Glucose
  • Immunoglobulin G
  • Insulin
  • Streptozocin