Pancreatic function in carboxyl-ester lipase knockout mice.
OBJECTIVE
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, α- and β-islet cells appeared morphologically normal and pancreatic exocrine function was also normal.


CONCLUSIONS
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. and IAP.
Vesterhus
Mette
M
Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Raeder
Helge
H
Kurpad
Amarnath J
AJ
Kawamori
Dan
D
Molven
Anders
A
Kulkarni
Rohit N
RN
Kahn
C Ronald
CR
Njølstad
Pål Rasmus
PR
D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism; D005951:Glucose Tolerance Test; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007408:Intestinal Absorption / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology*; D008049:Lipase / Q000502:physiology*; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046790:Pancreas, Exocrine / Q000166:cytology / Q000201:enzymology*; D015430:Weight Gain / Q000235:genetics
D001786:Blood Glucose; D008049:Lipase