The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Salk Institute for Biological Studies · Beth Israel Deaconess Medical Center · +6 more institutions
Abstract
The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which in turn drives gluconeogenesis. Adenoviral small…
Citation impact
- FWCI
- 28.68
- Percentile
- 100%
- References
- 49
Authors
8- RJReuben J. ShawCorresponding
Salk Institute for Biological Studies, Beth Israel Deaconess Medical Center, Harvard University, Torrey Pines Institute For Molecular Studies, Massachusetts General Hospital, Center for Systems Biology, Sungkyunkwan University
- KLKatja Lamia
Salk Institute for Biological Studies, Beth Israel Deaconess Medical Center, Harvard University, Torrey Pines Institute For Molecular Studies, Massachusetts General Hospital, Center for Systems Biology, Sungkyunkwan University
- DSDebbie S. Vasquez
Salk Institute for Biological Studies, Beth Israel Deaconess Medical Center, Harvard University, Torrey Pines Institute For Molecular Studies, Massachusetts General Hospital, Center for Systems Biology, Sungkyunkwan University
- SKSeung‐Hoi Koo
Salk Institute for Biological Studies, Beth Israel Deaconess Medical Center, Harvard University, Torrey Pines Institute For Molecular Studies, Massachusetts General Hospital, Center for Systems Biology, Sungkyunkwan University
- NBNabeel Bardeesy
Salk Institute for Biological Studies, Beth Israel Deaconess Medical Center, Harvard University, Torrey Pines Institute For Molecular Studies, Massachusetts General Hospital, Center for Systems Biology, Sungkyunkwan University
Topics & keywords
- AMPK
- Gluconeogenesis
- Endocrinology
- AMP-activated protein kinase
- Glucose homeostasis
- Internal medicine
- Protein kinase A
- Coactivator
- Good health and well-being