HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M600319-JLR200v1 48/1/207    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaster, M. Search for Related Content PubMed PubMed Citation Articles by Gaster, M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 48, 207-217, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Metabolic flexibility is conserved in diabetic myotubes

Michael Gaster¹

Molecular Endocrinology Unit, Department of Endocrinology, Odense University Hospital, Odense, Denmark

Published, JLR Papers in Press, October 24, 2006.

¹ To whom correspondence should be addressed. e-mail: michael.gaster{at}ouh.fyns-amt.dk

ABSTRACT

The purpose of this study was to test the hypothesis that metabolic inflexibility is an intrinsic defect. Glucose and lipid oxidation were studied in human myotubes established from healthy lean and obese subjects and patients with type 2 diabetes (T2D). In lean myotubes, glucose oxidation is raised by increasing glucose concentrations (0–20 mmol/l) and acute insulin stimulation (P < 0.05), whereas it is inhibited by palmitate (PA). PA oxidation is raised by increasing PA concentrations (0–0.6 mmol/l), whereas 1.0 mmol/l PA inhibits its own oxidation (P < 0.05). Furthermore, PA oxidation is increased by acute insulin stimulation (P < 0.05) and inhibited by glucose. Even 0.05 mM PA and 2.5 mM glucose significantly reduce glucose and PA oxidation (P < 0.05), respectively. Glucose and PA oxidation are insulin-sensitive in myotubes established from lean (46% and 17% glucose and PA oxidation, respectively; P < 0.05 vs. basal), obese (31% and 14%; P < 0.05), and T2D (17% and 8%; P < 0.05) subjects. PA supplementation reduces both basal and insulin-stimulated glucose oxidation by 33–44% (P < 0.05), and myotubes are still insulin-sensitive in all three groups (P < 0.05). Therefore, the metabolic inflexibility described in obese and diabetic patients is not an intrinsic defect; rather, it is based on an extramuscular mechanism (i.e., the inability to vary extracellular fatty acid concentrations during insulin stimulation). Thus, skeletal muscles are metabolic-flexible per se.

Supplementary key words fuel selection • glucose oxidation • insulin resistance • lipid oxidation • metabolic inflexibility • skeletal muscle • type 2 diabetes

Abbreviations: CPT1, carnitine palmitoyltransferase-1; FCS, fetal calf serum; PA, palmitate; PDH, pyruvate dehydrogenase; T2D, type 2 diabetes

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. E. Osler and J. R. Zierath Minireview: Adenosine 5'-Monophosphate-Activated Protein Kinase Regulation of Fatty Acid Oxidation in Skeletal Muscle Endocrinology, March 1, 2008; 149(3): 935 - 941. [Abstract] [Full Text] [PDF]