The role of glucokinase and insulin receptor substrate-2 in the proliferation of pancreatic beta cells induced by short-term high-fat diet feeding in mice
The role of glucokinase and insulin receptor substrate-2 in the proliferation of pancreatic beta cells induced by short-term high-fat diet feeding in mice
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DOI：
10.1016/j.metabol.2018.03.010
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发表时间：
2018-08-01
影响因子：
9.8
通讯作者：
Atsumi, Tatsuya
中科院分区：
文献类型：
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作者：
Kitao, Naoyuki;Nakamura, Akinobu;Atsumi, Tatsuya
目标：我们调查是否葡萄糖激酶和胰岛素受体底物-2所需的β细胞增殖诱导的短期高脂（HF）饮食喂养，已被证明为长期HF diet.Methods：8周龄的C57 BL/6 J小鼠暴露于一个标准的食物（SC）或HF饮食。饮食1周后，检查分离的胰岛中的组织病理学β细胞增殖和基因表达。此外，8周龄β细胞特异性葡萄糖激酶单倍不足（Gck（+/-））和Irs 2基因敲除（Irs 2（-/-））小鼠暴露于SC或HF diet.Results：免疫组织化学分析显示，短期HF饮食喂养导致BrdU掺入率显着增加相比，野生型小鼠SC消费。Western印迹分析表明，Irs 2的表达水平没有两种饮食之间的差异。此外，在Gck（+/-）和Irs 2（-/-）小鼠中，HF饮食组中的BrdU掺入率与SC组相比显著增加。从喂食HF饮食1周的小鼠分离的胰岛的基因表达谱显示Foxm 1的下游基因的表达水平协同上调。一周的HF饮食喂养刺激β细胞增殖与Foxm 1上调48周龄的小鼠，以及在8周龄。结论：短期HF饮食喂养诱导的小鼠胰腺β细胞增殖的机制可能涉及葡萄糖激酶和Irs 2的非依赖性途径。我们的研究结果表明，短期HF饮食喂养诱导β细胞增殖的途径可能不同于持续HF饮食喂养。(C)2018由Elsevier Inc.出版
Objective: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet.Methods: Eight-week-old C57BL/6J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient(Gck(+/-)) and Irs2 knockout (Irs2(-/-)) mice were exposed to either an SC or HF diet.Results: lmmunohistochemical analysis revealed that short-term HF diet feeding resulted in a significant increase in BrdU incorporation rate compared with SC consumption in wild-type mice. Western blot analysis demonstrated that Irs2 expression levels did not differ between the two diets. Moreover, there was a significant increase in the BrdU incorporation rate in the HF diet group compared with the SC group in both Gck(+/-) and Irs2(-/-) mice. Gene expression profiling of isolated islets from mice fed an HF diet for 1 week revealed that the expression levels of downstream genes of Foxm1 were coordinately upregulated. One week of HF diet feeding stimulated beta cell proliferation with Foxm1 upregulation in 48-week-old mice as well as in 8-week-old.Conclusions: The mechanism of pancreatic beta cell proliferation induced by short-term HF diet feeding in mice could involve a glucokinase- and Irs2-independent pathway. Our results suggest that the pathways that induce beta cell proliferation in response to short-term HF diet feeding may differ from those in response to sustained HF diet feeding. (C) 2018 Published by Elsevier Inc.