STRUCTURE AND ULTRASTRUCTURE OF THE ENDOC RINE PANCREAS IN DIABETIC TRANSGENIC MICE

The aim of the present study was to confirm the structural changes and to establish the ultrastructural alterations that occur in the endocr ine pancreas of mice with an induced insulin-dependent diabetes mellit us (IDDM) syndrome. For that purpose, we used transgenic mice (OVE 27) that overexpress a calmodulin gene in the beta cells of the endocrine pancreas. In these animals, the excess of calmodulin decreases the cy tosolic calcium levels in beta cells, leading to morphological and fun ctional alterations that produce a severe IDDM. Sections of pancreas ( tail) from 4 male 5-week-old diabetic mice (glycemia: 376 +/- 2 mg/dl) and from 4 normal age-matched males (glycemia: 113 +/- 13 mg/dl) were processed. Light microscopic immunohistochemical observations confirm ed a decrease in the number and size of pancreatic islets in transgeni c mice, together with a disruption in their architecture, without an a ssociated inflammatory response. The ultrastructural studies revealed diverse degrees of injury in the beta cells, such as the presence of m embrane interdigitations and alterations in their organelles and secre tory granules. These findings are in agreement with the quantitative a nd functional impairment of beta cells, coexisting with a normal appea rance of non-beta cell populations within the pancreatic islets. Our r esults demonstrate the existence of ultrastructural changes in the pan creatic beta cells of the experimental model studied. Such changes, to gether with the immunohistochemical alterations previously described, contribute to explain the appearance of a diabetic syndrome in these a nimals.