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首页> 美国卫生研究院文献>other >Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies
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Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies

机译：高脂饮食喂养的C57BL / 6NN和C57BL / 6NJ小鼠的胰岛素分泌差异：混合遗传背景在代谢研究中的意义。

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Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.
机译：许多新陈代谢研究都采用组织特异性基因敲除小鼠，这需要繁育的亚麻基因小鼠（大多在C57BL / 6N（NN）遗传背景下才能获得）和cre或Flp重组酶表达的小鼠在C57BL / 6J（JJ）背景下得到，导致生成混合C57BL / 6NJ（NJ）遗传背景小鼠。最近对NN和JJ菌株之间许多遗传差异的认识，包括烟酰胺核苷酸转氢酶（nnt）的缺失，需要检查混合NJ背景对葡萄糖耐量，β细胞功能和其他代谢参数的影响。对具有NN和NJ遗传背景的雄性小鼠喂食正常或高脂饮食（HFD）12周，并研究了葡萄糖和胰岛素的体内稳态。基因型对饲喂正常或高脂饮食的小鼠的体重和食物摄入没有影响。尽管HFD喂养的NJ小鼠的血糖和胰岛素敏感性与NN小鼠相似，但在进食和禁食状态以及葡萄糖激发后的胰岛素血症较低。 NJ小鼠表现出轻度的葡萄糖耐受不良。此外，在喂食HFD的NJ与NN小鼠中，分离的胰岛中葡萄糖而非KCl刺激的胰岛素分泌减少，而胰岛素含量和β细胞量却没有改变。在正常饮食下，除了减少进食的胰岛素血症外，NN和NJ小鼠具有相似的代谢参数。但是，与NN小鼠相比，HFD喂养的NJ小鼠体内和离体显示出较低的进食和禁食胰岛素血症以及葡萄糖诱导的胰岛素分泌。这些结果强烈警告不要使用不匹配的混合遗传背景C57BL / 6小鼠进行比较，尤其是在HFD条件下。

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