LKB1: a sweet side to Peutz-Jeghers syndrome?
LKB1: a sweet side to Peutz-Jeghers syndrome?
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DOI：
10.1016/j.molmed.2006.02.003
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发表时间：
2006-04-01
影响因子：
13.6
通讯作者：
Carling, David
中科院分区：
文献类型：
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作者：
Carling, David
最近发现肿瘤抑制因子 LKB1 是 AMP 激活蛋白激酶 (AMPK) 级联中的上游激酶，这提供了能量代谢与癌症之间的分子联系。 Shaw 及其同事最近的一项研究阐明了 LKB1 在 2 型糖尿病中的作用。肝脏中编码 LKB1 的基因缺失会导致糖异生基因表达和肝葡萄糖输出增加，从而导致明显的高血糖。重要的是，肝脏中 LKB1 的缺失消除了二甲双胍（一种广泛用于治疗 2 型糖尿病的药物）引起的降低血糖水平的作用。这些发现应该有助于解开围绕二甲双胍功能的谜团，该谜团已经持续了 30 年以上。
The recent discovery that the tumour suppressor LKB1 is an upstream kinase in the AMP-activated protein kinase (AMPK) cascade provided a molecular link between energy metabolism and cancer. A recent study by Shaw and colleagues elucidated the role of LKB1 in type 2 diabetes. Deletion of the gene encoding LKB1 in the liver leads to marked hyperglycaemia as a consequence of increased gluconeogenic gene expression and hepatic glucose output. Importantly, the absence of LKB1 in the liver abolishes the effect of lowering glucose level caused by metformin, a drug that is widely used for the treatment of type 2 diabetes. These findings should help solve the mystery surrounding the function of metformin, which has lasted for >30 years.