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Diabetologia：胰腺中O-GlcNAcylation具有多种代谢作用，但对小鼠胰岛素敏感器官的作用有限

2017-09-30 MedSci MedSci原创

O-GlcNAcylation胰岛素敏感器官
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近日，国际杂志 《Diabetologia》上在线发表一项关于胰腺中O-GlcNAcylation具有多种代谢作用，但对小鼠胰岛素敏感器官的作用有限的研究。

近日，国际杂志 《Diabetologia》上在线发表一项关于胰腺中O-GlcNAcylation具有多种代谢作用，但对小鼠胰岛素敏感器官的作用有限的研究。

O-GlcNAcylation的特征在于通过O- GlcNAc转移酶（OGT）向各种蛋白质中加入N-乙酰葡糖胺，并通过调节各种细胞过程来用于感应细胞内营养物质。虽然已经推测O- GlcNAcylation与葡萄糖代谢相关，但其在全身葡萄糖代谢中的确切作用尚未完全阐明。在这里，研究人员调查了在生理条件下， O-GlcNAcylation减少是否影响哺乳动物特定器官中的葡萄糖代谢。

通过用R26-Cre-ER T2小鼠杂交Ogt-flox小鼠产生他莫昔芬诱导的Ogt-Knockout（Ogt-KO）小鼠。分别通过用Ogt-flox和Alb-Cre，Mlc1f-Cre，Adipoq-Cre和Pdx1 PB- Creer TM小鼠杂交来产生肝脏，骨骼肌，脂肪组织和胰腺β细胞特异性Ogt-KO小鼠。葡萄糖代谢通过i.p葡萄糖和胰岛素耐量测试进行评估。

他莫昔芬诱导Ogt-KO小鼠在注射后4周显示致死表型，表明O-GlcNAcylation对于成年小鼠的存活是必不可少的。胰岛素敏感性器官（包括肝脏，骨骼肌和脂肪组织）的组织特异性Ogt缺失对生理条件下的葡萄糖代谢影响不大。然而，胰腺细胞特异性的β OGT -KO小鼠显示短暂低血糖（OGT -flox 5.46±0.41 VS OGT -βKO3.88±0.26毫摩尔/升）与约超2倍的胰岛素分泌和加速的肥胖相关，随后出现后续伴有胰岛素消耗的高血糖症（OGT-FLOX 6.34±0.32 VS OGT-βKO26.4±2.37mmol/l）并伴随着β细胞凋亡。

这些研究结果表明，O-GlcNAcylation对胰岛素敏感组织中的葡萄糖代谢影响不大，但在胰腺β细胞功能和生理条件下存活都起关键作用。研究结果为O-GlcNAc生物学和葡萄糖代谢生理学提供了新的见解。

原始出处：

Shogo Ida, Katsutaro Morino, Osamu Sekine,et al. Diverse metabolic effects of O-GlcNAcylation in the pancreas but limited effects in insulin-sensitive organs in mice

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    2018-06-14 baoya

    #胰岛#

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    2018-04-21 juliusluan78

    #胰岛素敏感#

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    2018-02-26 ms9608593228839890

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    2017-09-30 131****1460

    学习了受益匪浅

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