Impaired activation of AMP-Kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics

Chen, Michael B., McAinch, Andrew J., Macauley, S. Lance, Castelli, Laura A., O`Brien, Paul E., Dixon, John B., Cameron-Smith, David, Kemp, Bruce E. and Steinberg, Gregory R. 2005, Impaired activation of AMP-Kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics, Journal of clinical endocrinology & metabolism, vol. 90, no. 6, pp. 3665-3672.

Attached Files
Name Description MIMEType Size Downloads

Title Impaired activation of AMP-Kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics
Author(s) Chen, Michael B.
McAinch, Andrew J.
Macauley, S. Lance
Castelli, Laura A.
O`Brien, Paul E.
Dixon, John B.
Cameron-Smith, David
Kemp, Bruce E.
Steinberg, Gregory R.
Journal name Journal of clinical endocrinology & metabolism
Volume number 90
Issue number 6
Start page 3665
End page 3672
Publisher Endocrine Society
Place of publication Baltimore, Md
Publication date 2005-06
ISSN 0021-972X
1945-7197
Summary Adiponectin is an adipocyte-derived hormone associated with antidiabetic actions. In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2. In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects. Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052). In lean myotubes, gAD activates AMPK[alpha]1 and -[alpha]2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACC[beta]) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside. In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 [mu]g/ml) was blunted, but higher concentrations (0.5 [mu]g/ml) stimulated AMPK[alpha]1 and -[alpha]2 activities, AMPK and ACC[beta] phosphorylation, and fatty acid oxidation. In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPK[alpha]1 activity and AMPK phosphorylation; however, ACC[beta] phosphorylation and fatty acid oxidation were unaffected. Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPK[alpha] and ACC[beta] or the expression and activity of the upstream AMPK kinase, LKB1. These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
Language eng
Field of Research 110306 Endocrinology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2005, Endocrine Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006503

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 105 times in TR Web of Science
Scopus Citation Count Cited 113 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 464 Abstract Views, 0 File Downloads  -  Detailed Statistics
Created: Thu, 31 Jul 2008, 10:40:17 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.