Pancreatic Function in Carboxyl-Ester Lipase Knockout Mice
Pancreatic Function in Carboxyl-Ester Lipase Knockout Mice
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DOI：
10.1159/000266284
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发表时间：
2010-01-01
期刊：
影响因子：
3.6
通讯作者：
Njolstad, Pal Rasmus
中科院分区：
文献类型：
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作者：
Vesterhus, Mette;Raeder, Helge;Njolstad, Pal Rasmus
背景/目的：CEL-MODY是一种单基因形式的糖尿病和胰腺外分泌功能不全，其原因是羧酸酯脂肪酶(CEL)基因突变。本研究旨在研究CEL基因敲除小鼠(CELKO)的内分泌和外分泌胰腺功能。方法：对CEL基因敲除小鼠模型进行生理学和组织病理学研究，并与7个月和12个月龄的对照小鼠CEL+/+小鼠进行比较。结果：喂饲CELKO+/+和-/-小鼠生长发育正常，糖代谢正常。另一方面，服用60%高脂饮食的雌性CEL-/-小鼠，与产仔对照组相比，随机血糖升高(p=0.02)，并伴随着葡萄糖耐量的下降，但没有达到统计学意义。这些小鼠也有胰岛增生，但胰岛细胞形态正常，胰腺外分泌功能也正常。结论：虽然我们在CEL全身敲除的雌性小鼠中观察到了轻微的葡萄糖耐量异常，但并没有复制出人CEL-MODY的全部表型，这表明所涉及的致病机制比简单的CEL功能丧失更复杂。版权所有(C)2010 S.Karger AG，巴塞尔和IAP
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, alpha- and beta-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 (C) 2010 S. Karger AG, Basel and IAP