Regulation of Glucose Metabolism by Contractile Activity in Human Skeletal Muscle Myotubes from Severely Obese Individuals

Abstract

IntroductionExercise/ or contractile activity can enhance insulin sensitivity and oxidative capacity in skeletal muscle. However, the effects of contractile activity in skeletal muscle from severely obese individuals still remain unestablished.PurposeWe investigated insulin‐stimulated glucose metabolism in primary skeletal muscle myotubes from severely obese individuals (BMI ≥ 40 kg/m2) in response to contractile activity induced by electrical pulse stimulation.MethodFully mature myotubes from lean (BMI: 23.1 ± 0.7 kg/m2) and obese (BMI: 44.9± 2.5 kg/m2) individuals were stimulated for 24‐hours by applying an electrical pulse at 11.5 V, 1 Hz and 2 ms. Following contraction, insulin was added to examine the combined effects of muscle contraction and insulin on anabolic signaling.ResultIn myotubes from the severely obese individuals, insulin‐stimulated glycogen synthesis and glucose oxidation were normalized to the levels seen in muscle from the lean subjects without electrical stimulation. However, responses to electrical stimulation were blunted in the severely obese vs. lean subjects in terms of the magnitude of the improvements in insulin‐stimulated glucose metabolism. In addition, electrical stimulation increased insulin‐stimulated lactate production in severely obese but not lean subjects. Electrical stimulation increased adenosine monophosphate (AMP) accumulation and AMP‐activated protein kinase (AMPK) signaling, but to a lesser degree in myotubes from the severely obese donors. Electrical stimulation provided an improvement in insulin signal transduction in lean but not severely obese individuals. Especially, sites on AS160 phosphorylation (T642, S588, S341) showed enhanced response to electrical stimulation in lean but no changes in severely obese individuals.ConclusionThese data reveal that in the skeletal muscle of severely obese individuals, contractile activity can improve insulin‐stimulated glucose metabolism independent of insulin signaling. In addition, transient increase in AMPK signaling by accumulation of AMP for contractile activity appears to play a critical role in enhancing glucose metabolism in severely obese individual in response to electrical stimulation.Support or Funding InformationDK56112