AJP - Endo Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Endocrinol Metab 293: E172-E181, 2007. First published March 20, 2007; doi:10.1152/ajpendo.00677.2006
0193-1849/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/1/E172    most recent
00677.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smith, A. C.
Right arrow Articles by Dyck, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, A. C.
Right arrow Articles by Dyck, D. J.

Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia

Angela C. Smith,1 Kerry L. Mullen,1 Kathryn A. Junkin,1 Jennifer Nickerson,1 Adrian Chabowski,2 Arend Bonen,1 and David J. Dyck1

1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and 2Medical University of Bialystok, Bialystok, Poland

Submitted 12 December 2006 ; accepted in final form 14 March 2007

Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 ± 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats (P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha}, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle.

Zucker diabetic fatty rat; lipid metabolism; glucose transport; diacylglycerol; ceramide; adenosine 5'-monophosphate-activated protein kinase



Address for reprint requests and other correspondence: D. J. Dyck, Dept. of Human Health and Nutritional Sciences, Univ. of Guelph, Guelph, Ontario, Canada N1G 2W1 (e-mail: ddyck{at}uoguelph.ca)




This article has been cited by other articles:


Home page
Eur J EndocrinolHome page
E. Diamanti-Kandarakis, C. D Christakou, E. Kandaraki, and F. N Economou
Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome
Eur. J. Endocrinol., February 1, 2010; 162(2): 193 - 212.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
J. F. C. Glatz, J. J. F. P. Luiken, and A. Bonen
Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease
Physiol Rev, January 1, 2010; 90(1): 367 - 417.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Bonen, G. P. Holloway, N. N. Tandon, X.-X. Han, J. McFarlan, J. F. C. Glatz, and J. J. F. P. Luiken
Cardiac and skeletal muscle fatty acid transport and transporters and triacylglycerol and fatty acid oxidation in lean and Zucker diabetic fatty rats
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R1202 - R1212.
[Abstract] [Full Text] [PDF]


Home page
Eur J EndocrinolHome page
S. B Haugaard, H. Mu, A. Vaag, and S. Madsbad
Intramyocellular triglyceride content in man, influence of sex, obesity and glycaemic control
Eur. J. Endocrinol., July 1, 2009; 161(1): 57 - 64.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J. G. Nickerson, H. Alkhateeb, C. R. Benton, J. Lally, J. Nickerson, X.-X. Han, M. H. Wilson, S. S. Jain, L. A. Snook, J. F. C. Glatz, et al.
Greater Transport Efficiencies of the Membrane Fatty Acid Transporters FAT/CD36 and FATP4 Compared with FABPpm and FATP1 and Differential Effects on Fatty Acid Esterification and Oxidation in Rat Skeletal Muscle
J. Biol. Chem., June 12, 2009; 284(24): 16522 - 16530.
[Abstract] [Full Text] [PDF]


Home page
J. Lipid Res.Home page
A. Bonen, X.-X. Han, N. N. Tandon, J. F. C. Glatz, J. Lally, L. A. Snook, and J. J. F. P. Luiken
FAT/CD36 expression is not ablated in spontaneously hypertensive rats
J. Lipid Res., April 1, 2009; 50(4): 740 - 748.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. A. Junkin, D. J. Dyck, K. L. Mullen, A. Chabowski, and A. B. Thrush
Resistin acutely impairs insulin-stimulated glucose transport in rodent muscle in the presence, but not absence, of palmitate
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R944 - R951.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. L. Mullen, J. Pritchard, I. Ritchie, L. A. Snook, A. Chabowski, A. Bonen, D. Wright, and D. J. Dyck
Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high-fat-fed rats
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R243 - R251.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
N. Fujii, R. C. Ho, Y. Manabe, N. Jessen, T. Toyoda, W. L. Holland, S. A. Summers, M. F. Hirshman, and L. J. Goodyear
Ablation of AMP-Activated Protein Kinase {alpha}2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice
Diabetes, November 1, 2008; 57(11): 2958 - 2966.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. E. Pandke, K. L. Mullen, L. A. Snook, A. Bonen, and D. J. Dyck
Decreasing intramuscular phosphagen content simultaneously increases plasma membrane FAT/CD36 and GLUT4 transporter abundance
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R806 - R813.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
C. Moro, S. Bajpeyi, and S. R. Smith
Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity
Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E203 - E213.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.