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LKB1: a sweet side to Peutz-Jeghers syndrome?
1Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. dcarling@imperial.ac.uk
Abstract:
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.
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