Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3317440 | Pancreatology | 2010 | 10 Pages |
Abstract
Background/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 CEL knockout mice (CELKO). Methods: A knockout mouse model with global targeted deletion of CEL was 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, a- 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, thefull phenotype of human CEL-MODY was not reproduced, suggesting that the pathogenic mechanisms involved are more complex than a simple loss of CEL function.
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Authors
Mette Vesterhusa, Helge Rædera, Amarnath J. Kurpad, Dan Kawamori, Anders Molven, Rohit N. Kulkarni, C. Ronald Kahn, Pål Rasmus Njølstad,