Article
The MDM2-p53-pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells.
Nature communications - 6 Jun 2016
Li Xiaomu, Cheng Kenneth K Y, Liu Zhuohao, Yang Jin-Kui, Wang Baile, Jiang Xue, Zhou Yawen, Hallenborg Philip, Hoo Ruby L C, Lam Karen S L, Ikeda Yasuhiro, Gao Xin, Xu Aimin
Abstract excerpt
Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria. Here we show that the activation of p53 in β-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs GSIS, leading to glucose intolerance...
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