Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice.
Uncoupling protein-2 modulates the lipid metabolic response to fasting in mice.
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DOI：
10.1152/ajpgi.00016.2008
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发表时间：
2008-04
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通讯作者：
Anthony R Sheets;P. Fülöp;Zoltán Derdák;Andrea Kassai;E. Sabo;N. Mark;G. Paragh;J. Wands;G. Baff
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文献类型：
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作者：
Anthony R Sheets;P. Fülöp;Zoltán Derdák;Andrea Kassai;E. Sabo;N. Mark;G. Paragh;J. Wands;G. Baff
解偶联蛋白-2（UCP 2）通过控制β细胞中的ATP水平来调节胰岛素分泌。尽管UCP 2缺乏可改善小鼠的血糖控制，但UCP 2表达增加会干扰葡萄糖刺激的胰岛素分泌。这些观察结果将UCP 2与2型糖尿病中的β细胞功能障碍联系起来，具有令人困惑的进化作用。我们在禁食的ucp 2（-/-）小鼠中发现了更高的残留血清胰岛素水平和钝化的脂质代谢反应，这支持了UCP 2在饥饿期间进化为抑制胰岛素作用并适应燃料转换为脂肪酸的概念。在不存在UCP 2的情况下，禁食最初以低于预期的速率促进外周脂解和肝脏脂肪蓄积，但最终导致长期脂肪变性，表明肝脏利用和脂肪酸清除减少。我们的结论是，UCP 2介导的胰岛素分泌控制是一个生理相关的代谢反应禁食机制。
Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in beta-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to beta-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2(-/-) mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates but culminates in protracted steatosis, indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting.