Pancreatic Function in Carboxyl-Ester Lipase Knockout Mice

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 10; no. 4; pp. 467 - 476
• Main Authors: Vesterhusa, Mette, Rædera, Helge, Kurpad, Amarnath J, Kawamori, Dan, Molven, Anders, Kulkarni, Rohit N, Ronald Kahn, C, Rasmus Njølstad, Pål
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Elsevier B.V 01-10-2010; Elsevier Limited; S. Karger AG
• Subjects: Animals; Blood Glucose - genetics; Carboxyl-ester lipase; Disease Models, Animal; Endocrinology & Metabolism; Exocrine dysfunction; Female; Gastroenterology and Hepatology; Glucagon-Secreting Cells - cytology; Glucagon-Secreting Cells - metabolism; Glucose Tolerance Test; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Intestinal Absorption - genetics; Islets of Langerhans - cytology; Islets of Langerhans - enzymology; Lipase - physiology; Longevity - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MODY; Original Paper; Pancreas, Exocrine - cytology; Pancreas, Exocrine - enzymology; Weight Gain - genetics; Exocrine dysfunction; Carboxyl-ester lipase; MODY
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1159/000266284

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.