Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass.
Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass.
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发表时间：
2006
期刊：
影响因子：
30.8
通讯作者：
Naoko Hashimoto;Y. Kido;T. Uchida;Shun-ichiro Asahara;Yutaka Shigeyama;Tomokazu Matsuda;Akihiko Takeda;D. Tsuchihashi;Akihiko Nishizawa;W. Ogawa;Yoshito Fujimoto;H. Okamura;K. Arden;P. Herrera;T. Noda;M. Kasuga
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作者：
Naoko Hashimoto;Y. Kido;T. Uchida;Shun-ichiro Asahara;Yutaka Shigeyama;Tomokazu Matsuda;Akihiko Takeda;D. Tsuchihashi;Akihiko Nishizawa;W. Ogawa;Yoshito Fujimoto;H. Okamura;K. Arden;P. Herrera;T. Noda;M. Kasuga
2型糖尿病患者胰岛的总质量减少，可能导致这种疾病的发病机制。虽然胰岛质量的调节是复杂的，但最近的研究表明包括胰岛素或胰岛素样生长因子-1受体、胰岛素受体底物和磷脂酰肌醇（PI）3-激酶的信号通路的重要性。3-磷酸肌醇依赖性蛋白激酶1（PDK 1）是一种丝氨酸-苏氨酸激酶，介导PI 3-激酶下游的信号传导。在这里，我们表明，在胰腺β细胞中缺乏PDK 1的小鼠（betaPdk 1-/-小鼠）由于胰岛质量的损失而发展为进行性高血糖症。小鼠显示出胰岛密度以及细胞数量和大小的减少。转录因子Foxo 1基因的单倍不足导致细胞数量显著增加，但细胞大小没有增加，并导致betaPdk 1-/-小鼠葡萄糖稳态恢复。这些结果表明，PDK 1在维持胰腺细胞质量和葡萄糖稳态中是重要的。
The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis.