Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice

Apoptosis appears to play an important role in the development of diabetes in the non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the manifestation of insulin dependent diabetes mellitus (IDDM) can als o affect the sympathochromaffin system, we analyzed the role of apoptosis a nd infiltration of the adrenal medulla as features of this autoimmune proce ss in parallel with the development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks were studied and compa red with control mice. Apoptosis was assessed by in situ end-labeling metho d and ultrastructural analysis. Adrenals were screened for lymphocytic infi ltration by conventional hematoxylin-eosin staining. Chromaffin cells were characterized by immunohistochemical staining against synaptophysin and tyr osine hydroxylase. Apoptotic nuclei were detected in all mice studied at a very low level, mai nly occuring within the connective tissue between medulla and cortex. The m aximum score was achieved at 3 weeks (1.91 +/- 0.48 apoptotic cells/1000 co unted cells; n = 4). There was no significant difference between NOD mice a nd control mice. No correlation could be found between blood glucose levels and apoptosis. On the ultrastructural level, apoptotic cells presented typ ical features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice nor in controls lymphocytic infiltration or fibrosis of the adren al was detected. Even NOD mice with overt diabetes did not exhibit morpholo gical signs of medullitis. In summary, no signs of immune destruction of th e adrenal medulla in NOD mice aged 3 to 30 weeks could be detected.