Enalapril malate (angiotensin-converting enzyme inhibitor) in drinking water reduces the expression of MHC I-K and II-A in the duodenal epithelia and delays the onset of type 1 diabetes in NOD mice.
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B593
Abstract ID: 7470
Presenting Author:
Masakazu Hattori , Research Fellow
Abstract:
The NOD mouse develops type 1 diabetes characterized by infiltrating immune cells into the pancreatic islets (insulitis). NOD mice develop insulitis as early as 5 days of age after birth. Duodenum is the major site for proliferating Th17 cells and controlling their functions (Fravell RA, Nature 2011). Angiotensin-converting enzyme (ACE) exists in the small intestine and plays a role as a peptidase in the antigen presenting process of the mucosal immune system.
To examine the role of ACE in the development of type 1 diabetes in NOD mice, ACE-inhibitors (enalapril maleate: EM, or captopril: CA) were dissolved in the drinking water at the concentration of 12.5 mg/ml and given daily to 28-day-old NOD females and males ad libitum (EM: 72 females and 52 males, CA:89 and 70, water control 120 and 87, respectively). The mice were screened for the development of diabetes for 120 days and subjected to the life table and histochemical analyses.
The EM-treat NOD mice showed a 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=0.04). The CA-treatment was ineffective to delay the onset of diabetes. Morphometric analysis showed more islets without insulitis in EM-treat females (0.64mg/pancreas, n=16) than in CA-treat (0.53mg, n=17) and control females (0.36mg, n=18). mRNA of MHC-K and A genes in the duodenum and I-K and II-A expression on the pancreatic lymphocytes were reduced in the EM-treat mice.
Enalapril malate (angiotensin-converting enzyme inhibitor) in drinking water reduces the expression of MHC I-K and II-A in the duodenal epithelia and delays the onset of type 1 diabetes in NOD mice.
Category
Late Breaking Abstracts