We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
LKB1 Is Required for AICAR-Induced Elevations in Hexokinase II Content in Skeletal Muscle.
- Authors
Thomson, David M.; Brown, Jacob D.; Kim, Hyung-Jun; Chesser, David G.; Fillmore, Natasha; Porter, Brian B.; Tall, James H.; Barrow, Jeffery R.; Winder, William W.
- Abstract
Chronic AICAR administration increases the content of hexokinase II (HKII) in type IIb skeletal muscle via phosphorylation and activation of 5′AMP-activated protein kinase (AMPK). LKB1 is the predominant AMPK kinase in skeletal muscle. While other potential AMPK kinases have been identified, their role in the regulation of AMPK in skeletal muscle remains obscure. Therefore, the purpose of this study was to determine whether LKB1 is necessary for the increase in HKII that occurs with chronic AICAR stimulation. Wild-type (WT) and skeletal muscle-specific LKB1-KO (KO) mice were injected subcutaneously once per day for 5 days with AICAR (0.5 mg/ g BW) or saline. White quadriceps muscles were removed from the mice 90 minutes after the final AICAR injection on day 5 and were subsequently homogenized and analyzed by western blotting. LKB1 concentration and AMPK phosphorylation at Thr172 were reduced by ∼96% in KO muscles compared to WT muscles, demonstrating the efficacy of the LKB1 knock-out. Neither LKB1 protein level or AMPK phosphorylation were affected by AICAR treatment. Nevertheless, phosphorylation of acetyl CoA carboxylase (a downstream target of AMPK), was increased by ∼200% in the WT, but not KO muscles, suggesting that in-vivo AMPK activity was indeed elevated by AICAR in a LKB1-dependent manner. HKII levels were increased by ∼150% with AICAR treatment in the WT muscles, but were unchanged in the KO muscles, demonstrating the necessity of LKB1 for AICAR-induced increases in HKII concentration.
- Subjects
PROTEIN kinases; GLUCOKINASE; MUSCLES; PHOSPHORYLATION; MICE
- Publication
Diabetes, 2007, Vol 56, pA63
- ISSN
0012-1797
- Publication type
Article