Authors:
Accalia Fu, Andy Cheuk-Him Ng, Chantal Depatie, Nadeeja Wijesekara, Ying He, Gen-Sheng Wang, Nabeel Bardeesy, Fraser W. Scott, Rhian M. Touyz, Michael B. Wheeler, and Robert A. Screaton
Summary:
The Lkb1 tumor suppressor exerts its biological effects through phosphorylation and consequent activation of the AMP kinase (AMPK) family. Extensive genetic and biochemical evidence supports a role for Lkb1 in cell cycle arrest, establishment of cell polarity, and cellular energy metabolism. However, the role of Lkb1 and the AMPK family in β cell function in vivo has not been established. We generated conditional knockout mice with a deletion of the Lkb1 gene in the β cell compartment of pancreatic islets; these mice display improved glucose tolerance and protection against diet-induced hyperglycemia. Lkb1−/− β cells are hypertrophic because of elevated mTOR activity; they also proliferate more and secrete more insulin in response to glucose. These data indicate that inhibiting Lkb1 activity in β cells may facilitate β cell expansion and glucose tolerance in vivo.
Source:
Cell Metabolism; Vol. 10, Issue 4, 285-295 (10/07/09)