title: Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise.
abstract: Exercise improves insulin sensitivity and oxidative capacity in skeletal muscles. However, the effect of exercise on substrate oxidation is less clear in obese and type 2 diabetic subjects than in lean subjects. We investigated glucose and lipid metabolism and gene expression after 48 h with low-frequency electrical pulse stimulation (EPS), as an in vitro model of exercise, in cultured myotubes established from lean nondiabetic subjects and severely obese subjects (BMI ≥ 40 kg/m(2)) with and without type 2 diabetes. EPS induced an increase in insulin sensitivity but did not improve lipid oxidation in myotubes from severely obese subjects. Thus, EPS-induced increases in insulin sensitivity and lipid oxidation were positively and negatively correlated to BMI of the subjects, respectively. EPS enhanced oxidative capacity of glucose in myotubes from all subjects. Furthermore, EPS reduced mRNA expression of slow fiber-type marker (MYH7) in myotubes from diabetic subjects; however, the protein expression of this marker was not significantly affected by EPS in either of the donor groups. On the contrary, mRNA levels of interleukin-6 (IL-6) and IL-8 were unaffected by EPS in myotubes from diabetic subjects, while IL-6 mRNA expression was increased in myotubes from nondiabetic subjects. EPS-stimulated mRNA expression levels of MYH7, IL-6, and IL-8 correlated negatively with subjects' HbA1c and/or fasting plasma glucose, suggesting an effect linked to the diabetic phenotype. Taken together, these data show that myotubes from different donor groups respond differently to EPS, suggesting that this effect may reflect the in vivo characteristics of the donor groups.
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway; y.z.feng@farmasi.uio.no.
authors.forename: Yuan Z
authors.initials: YZ
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;
authors.forename: Nataša
authors.initials: N
authors.lastname: Nikolić
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;
authors.forename: Siril S
authors.initials: SS
authors.lastname: Bakke
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;
authors.forename: Eili T
authors.initials: ET
authors.lastname: Kase
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;
authors.forename: Kari
authors.initials: K
authors.lastname: Guderud
authors.affiliation: The Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Jøran
authors.initials: J
authors.lastname: Hjelmesæth
authors.affiliation: Faculty of Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway; and.
authors.forename: Vigdis
authors.initials: V
authors.lastname: Aas
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000175:diagnosis / Q000378:metabolism*; D012720:Severity of Illness Index; D013851:Thinness / Q000175:diagnosis / Q000378:metabolism*
keywords: PPARδ activation; in vitro exercise model; insulin sensitivity; myotubes from severely obese subjects; oleic acid and glucose metabolism