LKB1: a sweet side to Peutz-Jeghers syndrome?

Trends Mol Med. 2006 Apr;12(4):144-7. doi: 10.1016/j.molmed.2006.02.003. Epub 2006 Mar 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Gluconeogenesis / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Metformin / pharmacology
  • Models, Biological
  • Multienzyme Complexes / metabolism
  • Peutz-Jeghers Syndrome / enzymology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*

Substances

  • Hypoglycemic Agents
  • Multienzyme Complexes
  • Metformin
  • STK11 protein, human
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases