Angiotensin-converting enzyme (ACE) exists in the kidney, lung and small intestine of the NOD mouse (autoimmune type 1 diabetes animal model). ACE changes Angiotensin I to Angiotensin II. ACE exists in the small intestinal epithelial cells and villi, and digests the protein antigen molecules in the small intestine. ACE plays an important role in the antigen presenting process in the mucosal immune system of the duodenum and jejunum. To examine if ACE has a role in the development of type 1 diabetes of the NOD mouse, ACE Inhibitors, enalapril maleate (EM) or captopril (CA) was dissolved in a drinking water at the concentration of 12.5μg/ml and given daily to 28-day-old NOD mice ad libitum (89 females and 70 males in CA, 72 and 52 in EM, 120 and 87 in water control group, respectively). The animals were screened for the development of diabetes twice a week for 7 months and subjected to the Life Table analysis. The incidence of diabetes in our NOD/Kmc colony is 83% in females and 40% in males at 210 days of age. The EM-treated NOD mice showed a significant delay of the onset of diabetes at 120 days of age in comparison with the controls (25% vs. 45% in females, P=0.002; 0% vs. 8% in males, P=0.037). The CA treatment was ineffective to delay the onset of diabetes. The histological examination of the pancreata showed that the EM-treated females had more islets without lymphocytic infiltration than the water-control females (mean number of undamaged islets±SD: 11.1±8.5 in EM vs. 1.9±2.5 in Control, P=0.009). The undamaged islets weighed 0.772±0.383 in EM and 0.441±0.386 in water-control (mg: mean±SE). The mRNA expression of MHC K and A genes was suppressed in the duodenum and jejunum of the NOD mice by EM- or CA-water for 14 days. Flow cytometric analysis showed suppression of the MHC K and I-A expression in the pancreatic lymphocytes of the EM- and CA-treated mice in comparison with the control mice.


M. Hattori: None. A. Ueda: None. R. Katoh: None. M. Hirai: None. A. Noda: None. K. Mayanagi: None. Y. Furuichi: None. K. Hattori: None. T. Lund: None. K. Kobayashi: None. Y. Nakamura: None.

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