Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver
Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver
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DOI：
10.1126/science.1163971
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发表时间：
2008-11-21
期刊：
影响因子：
56.9
通讯作者：
Oka, Yoshitomo
中科院分区：
文献类型：
--
作者：
Imai, Junta;Katagiri, Hideki;Oka, Yoshitomo
哺乳动物的代谢调节需要多个器官和组织之间的沟通。肥胖症和相关代谢紊乱（包括2型糖尿病）发病率的上升重新引起了对器官间通讯的兴趣。我们使用小鼠模型来探索肥胖增强胰腺β细胞质量的机制，这是对胰岛素抵抗的病理生理补偿。我们发现肝脏细胞外调节激酶（ERK）信号的激活通过神经元介导的代谢信号的传递诱导胰腺B细胞增殖。这种从肝脏到胰腺的代谢中继参与了肥胖诱导的胰岛扩张。在胰岛素缺乏型糖尿病的小鼠模型中，肝脏选择性激活ERK信号传导增加了B细胞质量并使血清葡萄糖水平正常化。因此，器官间代谢中继系统可以作为糖尿病再生治疗的有价值的目标。
Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic beta cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic b cell proliferation through a neuronal- mediated relay of metabolic signals. This metabolic relay from the liver to the pancreas is involved in obesity- induced islet expansion. In mouse models of insulin- deficient diabetes, liver- selective activation of ERK signaling increased b cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.