Metabolic flexibility is conserved in diabetic myotubes.
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.
Gaster
Michael
M
Molecular Endocrinology Unit, Department of Endocrinology, Odense University Hospital, Odense, Denmark. michael.gaster@ouh.fyns-amt.dk
D015992:Body Mass Index; D018929:Cell Culture Techniques; D003920:Diabetes Mellitus / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D012016:Reference Values
D005227:Fatty Acids; D005947:Glucose