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Glucose Metabolism is Impaired in Cultured Myotubes from Severely Obese Humans
Author(s) -
Zou Kai,
Hinkley J Matthew,
Billings Sarah,
Park Sanghee,
Zheng Donghai,
Jones Terry,
Hornsby Pamela,
Lenhard James,
Pories Walter,
Dohm G Lynis,
Houmard Joseph
Publication year - 2015
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.29.1_supplement.944.11
Subject(s) - myogenesis , medicine , endocrinology , skeletal muscle , carbohydrate metabolism , glycogen , insulin , metabolism , glycolysis , glycogen synthase , glucose uptake , insulin resistance , biology , chemistry
In vivo , severe obesity is associated with marked defects in skeletal muscle glucose metabolism. However, it is not evident if these metabolic defects are retained in human primary skeletal muscle cells (HSkMCs) raised in culture, which indicates a genetic and/or epigenetic influence. The purpose of this study was to determine whether impaired glucose metabolism is retained in differentiated myotubes established from severely obese subjects. HSkMCs obtained from lean (BMI = 23.9 ± 0.1 kg/m 2 ) and severely obese (BMI = 47.7 ± 0.6 kg/m 2 ) muscle biopsies were differentiated to myotubes. Radiolabeled 1‐ 14 C glucose was used to measure glycogen synthesis (GS), glucose oxidation (GO) and non‐oxidized glycolysis (NOG) rates in the presence or absence of insulin. Insulin‐stimulated GS and GO rates were elevated to greater extents in myotubes from lean subjects (33% and 17%) in comparison to the severely obese (18% and 6%). In contrast, NOG production did not change in myotubes from lean donors in response to insulin, but largely increased (26%) in severely obese, resulting in a decreased (16%) ratio of oxidized to non‐oxidized glucose in comparison to lean controls. In addition, glycogen synthesis rate was enhanced in myotubes from lean (32%) compared to severely obese (18%). These data suggest that myotubes established from severely obese humans have impaired glucose metabolism.