Premium
Roux‐en‐Y Gastric Bypass Surgery Enhances Contraction‐Mediated Glucose Metabolism in Primary Human Myotubes
Author(s) -
Hinkley J. Matthew,
Zou Kai,
Park Sanghee,
Turner Kristen,
Zheng Donghai,
Houmard Joseph A
Publication year - 2016
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.30.1_supplement.1014.3
Subject(s) - myogenesis , medicine , endocrinology , basal (medicine) , skeletal muscle , contraction (grammar) , stimulation , insulin , glycogen , glucose uptake , carbohydrate metabolism , glycogen synthase , insulin resistance , myocyte , glycolysis , muscle contraction , metabolism , biology
Contractile activity (e.g. exercise) invokes various metabolic adaptations in skeletal muscle, including improved insulin action and substrate oxidation. However, individuals with metabolic perturbations (i.e. severely obese (BMI ≥ 40 kg/m 2 ) and type 2 diabetics) appear to have inherent defects in the ability to respond to contractile activity. Along with significant weight loss, Roux‐en‐Y gastric bypass (RYGB) surgery elicits positive metabolic adaptations; however, it is uncertain whether this clinical intervention alters the myocellular milieu to respond to contractile activity. To examine this, skeletal muscle cells were isolated from muscle biopsies obtained from patients before and after RYGB surgery, and differentiated into myotubes. Once fully differentiated, myotubes were electrically stimulated to contract for 24 hours (2 ms bipolar pulse, 1 Hz, and 11.5 V), after which changes in metabolic function and intracellular signaling were examined. Myotubes from severely obese patients prior to RYGB surgery were unresponsive to the metabolic benefits of muscle contractile activity, as indicated by a lack of change in insulin‐stimulated glycogen synthesis (38.6% vs. 38.5% increase over basal for control vs. electrical stimulation) and basal glucose oxidation (4.5 nmol glucose/mg/hr vs. 4.6 nmol glucose/mg/hr control vs. electrical stimulation). Interestingly, myotubes derived from the same patients 1‐month post‐RYGB were responsive to muscle contraction, as indicated by an ~1.4‐fold increase in insulin‐stimulated glycogen synthesis (36.9% vs. 52.9% increase over basal for control vs. electrical stimulation) and an ~1.5‐fold increase in basal glucose oxidation (3.9 nmol glucose/mg/hr vs. 5.5 nmol glucose/mg/hr control vs. electrical stimulation). At the molecular level, while unresponsive before surgery, muscle contraction improved insulin‐stimulated phosphorylation of the Rab‐GTPase AS160 1‐month following RYGB surgery (~1.9‐fold vs. ~2.6‐fold insulin stimulation for control vs. electrical stimulation). These data indicate that RYGB surgery inherently improves the ability of skeletal muscle to respond to contractile activity, suggesting an exercise program should be immediately implemented in these patients to further improve substrate metabolism. Support or Funding Information NIH DK56112