Pancreatic Function in Carboxyl-Ester Lipase Knockout Mice

AbstractBackground/Aims:CEL-MODY is a monogenic form of diabetes and exocrine pancreatic insufficiency due to mutations in the carboxyl-ester lipase (CEL) gene. We aimed to investigate endocrine and exocrine pancreatic function in CELknockout mice (CELKO). Methods:A knockout mouse model with global targeted deletion of CELwas investigated physiologically and histopathologically, and compared to littermate control CEL+/+ mice at 7 and 12 months on normal chow and high-fat diets (HFD), i.e. 42 and 60 fat by calories. Results:CELKO+/+ and –/– mice showed normal growth and development and normal glucose metabolism on a chow diet. Female CEL–/– mice on 60 HFD, on the other hand, had increased random blood glucose compared to littermate controls (p = 0.02), and this was accompanied by a reduction in glucose tolerance that did not reach statistical significance. In these mice there was also islet hyperplasia, however, α- and β-islet cells appeared morphologically normal and pancreatic exocrine function was also normal. Conclusion: Although we observed mild glucose intolerance in female mice with whole-body knockout of CEL, the full phenotype of human CEL-MODY was not reproduced, suggesting that the pathogenic mechanisms involved are more complex than a simple loss of CEL function.Copyright © 2010 S. Karger AG, Basel and IAP