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Improved Insulin‐Mediated Glucose Oxidation in Cultured Human Myotubes Following Roux‐en‐Y Gastric Bypass Surgery
Author(s) -
Zou Kai,
Hinkley J. Matthew,
Park Sanghee,
Zheng Donghai,
Dohm G. Lynis,
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.770.4
Subject(s) - myogenesis , skeletal muscle , gastric bypass surgery , insulin , medicine , endocrinology , glycolysis , glucose uptake , insulin resistance , stimulation , gastric bypass , obesity , metabolism , weight loss
Roux‐en‐Y gastric bypass (RYGB) leads to remission of type 2 diabetes and markedly improved insulin‐mediated glucose oxidation at the whole body level, as well as in skeletal muscle. However, little is known about whether the improvements occur intrinsically at the level of skeletal muscle. The purpose of this study was to determine whether improved glucose oxidation is intrinsically retained in differentiated myotubes derived from RYGB surgery patients, and if so, the time course of the improvement. Primary human skeletal muscle cells were isolated from muscle biopsies obtained from 6 RYGB patients prior to, 1‐month and 7‐months following surgery (BMI = 50.2 ± 2.0, 43.2 ± 2.8 and 35.7 ± 2.2 kg/m 2 , respectively) and 6 lean subjects (BMI = 23.4 ± 0.6 kg/m 2 ) and were differentiated to myotubes. Radiolabeled 1‐ 14 C glucose was used to measure complete glucose oxidation (GO) and non‐oxidized glycolysis (NOG) rates in the presence or absence of insulin. Insulin‐stimulated GO rate was significantly elevated to greater extent in myotubes derived from RYGB patients at 1‐month after surgery in comparison to before surgery (7.3 ± 3.4% vs. −2.2 ± 2.3%, respectively, P<0.05). It was further enhanced at 7‐months post‐surgery (13.5 ± 2.1%, P<0.05), which was virtually restored to the level of lean people (15.4 ± 1.4%). On the other hand, NOG production in response to insulin stimulation was not significantly changed in myotubes from RYGB patients at 1‐months post‐surgery in comparison to before surgery (16.0 ± 6.2% vs. 19.5 ± 5.6%), but was largely decreased at 7‐months post‐surgery (−1.3 ± 3.6%, P<0.05), which was almost identical to the lean control group (−1.2 ± 2.5%). These changes lead to the improvement of GO/NOG ratio, an indicator of glucose partitioning, in response to insulin stimulation in myotubes from RYGB patients at both 1‐month (1.8 ± 3.8%, P=0.08) and 7‐months (11.2 ± 1.0%, P<0.05) post‐surgery when compared to before surgery (−10.8 ± 5.4%). Taken together, these data suggest that RYGB surgery can rapidly improve glucose oxidation intrinsically in skeletal muscle as early as 1‐month following surgery and further restore it to the level control level. Support or Funding Information National Institute of Health (DK 56112)