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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

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