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Increases in insulin signaling following electrical pulse stimulation are blunted in myotubes derived from severely obese individuals with or without type 2 diabetes
Author(s) -
LIM SEONGKYUN,
CHAVES ALEC,
ZHENG DONGHAI,
HOUMARD JOSEPH
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.603.18
Subject(s) - endocrinology , medicine , insulin , myogenesis , insulin resistance , skeletal muscle , stimulation , type 2 diabetes , diabetes mellitus , protein kinase b , biology , phosphorylation , microbiology and biotechnology
Exercise training has been shown to be effective in improving skeletal muscle insulin sensitivity, but individuals with severe obesity and/or type 2 diabetes (T2D) may not respond as robustly as lean individuals. Electrical pulse stimulation (EPS) applied to primary human skeletal muscle cell cultures (myotubes) has been used as an in vitro exercise model to understand responses to contractile activity alone. Purpose The purpose of this study was to examine the effect of antecedent EPS on insulin signaling in myotubes from lean and severely obese individuals, with and without type 2 diabetes. Methods Human muscle cells were cultured from muscle biopsies obtained from lean (BMI: 21.7± 0.75 kg/m 2 ), obese (BMI: 39.1± 0.99 kg/m 2 ), and diabetic (BMI: 40.7 ± 9.44 kg/m 2 ) individuals. Following differentiation, mature myotubes were stimulated with electrical pulses, set at 11.5 V, 1 Hz and 2 ms for 24 h. Following EPS, myotubes were treated with 100nM insulin for 10 minutes, after which the cell lysate was harvested for western blot analysis to measure the phosphorylation status of AKT (pAKT). Results Insulin stimulation increased pAKT levels in all three groups (p = 0.04, Mean ± SEM, 2.86 ± 0.43, 2.1 ± 0.33, 1.85 ± 0.12; fold change over control in lean, obese, and T2D respectively). However, in response to EPS, only the lean group increased insulin‐stimulated pAKT further (p=0.03, 2.86 ± 0.43 vs 4.07 ± 0.11, fold increase over control). Conclusion Our data show that EPS increases insulin‐stimulated pAKT levels in myotubes from lean individuals, but this response is absent in myotubes from individuals with severe obesity with or without T2D, indicating that there is an inherent defect in their cellular response to electrical/contractile activity. Support or Funding Information National Institutes of Health (DK56112, JAH).