Loss of Lkb1 in adult beta cells increases beta cell mass and enhances glucose tolerance in mice.
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 beta cell function in vivo has not been established. We generated conditional knockout mice with a deletion of the Lkb1 gene in the beta cell compartment of pancreatic islets; these mice display improved glucose tolerance and protection against diet-induced hyperglycemia. Lkb1(-/-) beta 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 beta cells may facilitate beta cell expansion and glucose tolerance in vivo.
Fu
Accalia
A
Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada.
Ng
Andy Cheuk-Him
AC
Depatie
Chantal
C
Wijesekara
Nadeeja
N
He
Ying
Y
Wang
Gen-Sheng
GS
Bardeesy
Nabeel
N
Scott
Fraser W
FW
Touyz
Rhian M
RM
Wheeler
Michael B
MB
Screaton
Robert A
RA
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004041:Dietary Fats; D004965:Estrogen Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D019076:Transgenes
D004041:Dietary Fats; D004965:Estrogen Antagonists; D007328:Insulin; D013629:Tamoxifen; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose