Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Pancreatology. 2010;10(4):467-76. doi: 10.1159/000266284. Epub 2010 Aug 19.
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).
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.
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.
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.
背景/目的：CEL-MODY 是一种由于羧基酯脂肪酶（CEL）基因突变导致的单基因糖尿病和外分泌胰腺功能不全。我们旨在研究 CEL 敲除小鼠（CELKO）的内分泌和外分泌胰腺功能。
我们对具有 CEL 基因全局靶向缺失的敲除小鼠模型进行了生理学和组织病理学研究，并与同窝对照 CEL+/+ 小鼠在正常饲料和高脂肪饮食（HFD）下（即 42%和 60%的卡路里来自脂肪）进行了比较，分别在 7 个月和 12 个月时进行了比较。
CELKO+/+ 和 -/- 小鼠在正常饮食下生长发育正常，葡萄糖代谢正常。然而，另一方面，雌性 CEL-/- 小鼠在 60%HFD 下随机血糖升高，与同窝对照相比（p=0.02），这伴随着葡萄糖耐量降低，但未达到统计学意义。在这些小鼠中还观察到胰岛增生，然而，α-和β-胰岛细胞形态正常，胰腺外分泌功能也正常。
尽管我们观察到全身敲除 CEL 的雌性小鼠存在轻度葡萄糖不耐受，但并未复制人类 CEL-MODY 的完全表型，这表明涉及的发病机制比单纯的 CEL 功能丧失更为复杂。
