In vitro contraction protects against palmitate-induced insulin resistance in C2C12 myotubes
| العنوان: | In vitro contraction protects against palmitate-induced insulin resistance in C2C12 myotubes |
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| المؤلفون: | Stephan Nieuwoudt, Ciaran E. Fealy, Elizabeth E. Martelli, Srinivasan Dasarathy, John P. Kirwan, Sathyamangla V. Naga Prasad, Anny Mulya |
| المصدر: | American Journal of Physiology-Cell Physiology. 313:C575-C583 |
| بيانات النشر: | American Physiological Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Contraction (grammar), Physiology, Muscle Fibers, Skeletal, Palmitates, 030209 endocrinology & metabolism, Type 2 diabetes, Biology, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Animals, Muscle, Skeletal, Myogenesis, Cell Biology, medicine.disease, Electric Stimulation, In vitro, 030104 developmental biology, Endocrinology, Cell culture, Insulin Resistance, C2C12, Muscle Contraction, Research Article |
| الوصف: | We are interested in understanding mechanisms that govern the protective role of exercise against lipid-induced insulin resistance, a key driver of type 2 diabetes. In this context, cell culture models provide a level of abstraction that aid in our understanding of cellular physiology. Here we describe the development of an in vitro myotube contraction system that provides this protective effect, and which we have harnessed to investigate lipid-induced insulin resistance. C2C12 myocytes were differentiated into contractile myotubes. A custom manufactured platinum electrode system and pulse stimulator, with polarity switching, provided an electrical pulse stimulus (EPS) (1 Hz, 6-ms pulse width, 1.5 V/mm, 16 h). Contractility was assessed by optical flow flied spot noise mapping and inhibited by application of ammonium acetate. Following EPS, myotubes were challenged with 0.5 mM palmitate for 4 h. Cells were then treated with or without insulin for glucose uptake (30 min), secondary insulin signaling activation (10 min), and phosphoinositide 3-kinase-α (PI3Kα) activity (5 min). Prolonged EPS increased non-insulin-stimulated glucose uptake (83%, P = 0.002), Akt (Thr308) phosphorylation ( P = 0.005), and insulin receptor substrate-1 (IRS-1)-associated PI3Kα activity ( P = 0.048). Palmitate reduced insulin-specific action on glucose uptake (−49%, P < 0.001) and inhibited insulin-stimulated Akt phosphorylation ( P = 0.049) and whole cell PI3Kα activity ( P = 0.009). The inhibitory effects of palmitate were completely absent with EPS pretreatment at the levels of glucose uptake, insulin responsiveness, Akt phosphorylation, and whole cell PI3Kα activity. This model suggests that muscle contraction alone is a sufficient stimulus to protect against lipid-induced insulin resistance as evidenced by changes in the proximal canonical insulin-signaling pathway. |
| تدمد: | 1522-1563 0363-6143 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e879a383ad398d8cb96ddc42d202893eTest https://doi.org/10.1152/ajpcell.00123.2017Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e879a383ad398d8cb96ddc42d202893e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
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