Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction
Research output: Contribution to journal › Journal article › Research › peer-review
Recent studies indicate that the LKB1 tumour suppressor protein kinase is the major 'upstream' activator of the energy sensor AMP-activated protein kinase (AMPK). We have used mice in which LKB1 is expressed at only ∼10% of the normal levels in muscle and most other tissues, or that lack LKB1 entirely in skeletal muscle. Muscle expressing only 10% of the normal level of LKB1 had significantly reduced phosphorylation and activation of AMPKα2. In LKB1-lacking muscle, the basal activity of the AMPKα2 isoform was greatly reduced and was not increased by the AMP-mimetic agent, 5-aminoimidazole-4- carboxamide riboside (AICAR), by the antidiabetic drug phenformin, or by muscle contraction. Moreover, phosphorylation of acetyl CoA carboxylase-2, a downstream target of AMPK, was profoundly reduced. Glucose uptake stimulated by AICAR or muscle contraction, but not by insulin, was inhibited in the absence of LKB1. Contraction increased the AMP:ATP ratio to a greater extent in LKB1-deficient muscles than in LKB1-expressing muscles. These studies establish the importance of LKB1 in regulating AMPK activity and cellular energy levels in response to contraction and phenformin.
Original language | English |
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Journal | EMBO Journal |
Volume | 24 |
Issue number | 10 |
Pages (from-to) | 1810-1820 |
Number of pages | 11 |
ISSN | 0261-4189 |
DOIs | |
Publication status | Published - 18 May 2005 |
Externally published | Yes |
- AMP-activated protein kinase, Glucose transport, LKB1, Phenformin, Skeletal muscle
Research areas
ID: 239777070