Electrical pulse stimulation induces GLUT4 translocation in a Rac‐Akt‐dependent manner in C2C12 myotubes

Abstract

Muscle contraction increases skeletal muscle glucose uptake, but the underlying mechanisms are not fully elucidated. While important for insulin-stimulated glucose uptake, the role of Akt in contraction-stimulated muscle glucose uptake is controversial. In our study, C2C12 skeletal muscle myotubes were contracted by electrical pulse stimulation (EPS). We found that EPS leads to Akt phosphorylation on sites S473 and T308 in a time-dependent manner. The Akt inhibitor MK2206 partly reduces EPS-stimulated GLUT4 translocation without affecting EPS-stimulated AMPK phosphorylation. EPS activates Rac1 GTP-binding, and EPS-stimulated GLUT4 translocation is partly inhibited by Rac1 inhibitor II and siRac1. Interestingly, both Rac1 inhibitor II and siRac1 inhibit EPS-stimulated Akt phosphorylation on sites S473 and T308. Our findings implicate a Rac1-Akt signaling pathway in EPS-stimulated GLUT4 translocation in C2C12 myotubes.

Loss of TP53I11 Enhances the Extracellular Matrix‐independent Survival by Promoting Activation of AMPK

“…Otherwise, AKT/m‐TOR signaling pathway serves as a central regulator of cell growth, proliferation, survival, and metabolism . In this study, loss of TP53I11 promoted the activation of AKT/m‐TOR pathway, increased PGC‐1α expression and thereby enhanced OXPHOS in attach‐cultured MCF10A cells.…”

Electromyostimulation to fight atrophy and to build muscle: facts and numbers

“…The electrical stimulation of these cultures for up to 13 days (250 ms impulse trains of 40 Hz, repeated every 4 s) led to an isoform switch, as indicated by an increase in slow myosin expression. In recent years, several researchers have used C2C12 skeletal muscle myotubes electrically stimulated in cell culture allowing contraction‐inducible cellular responses to be explored . Using these models, contraction‐inducible myokines potentially linked to the metabolic alterations, immune responses, and angiogenesis induced by exercise could be identified .…”

“…In recent years, several researchers have used C2C12 skeletal muscle myotubes electrically stimulated in cell culture allowing contraction-inducible cellular responses to be explored. 10,11 Using these models, contraction-inducible myokines potentially linked to the metabolic alterations, immune responses, and angiogenesis induced by exercise could be identified. 12 It became clearly evident that electrical stimulation of cells resulted in an upregulation and activation of AMPK, JNK, Akt, eNOS, GLUT4, and PGC1.…”

“…12 It became clearly evident that electrical stimulation of cells resulted in an upregulation and activation of AMPK, JNK, Akt, eNOS, GLUT4, and PGC1. 11 Furthermore, it seems that the EMS-stimulated Glut4 translocation to the cell membrane is mediated via Rac1-Akt signaling 10 and that electrically stimulated cells are protected against lipid-induced insulin resistance. 13 Taken together, the electrical stimulation of cells in culture at least partially mirrors effects of exercise training seen in experimental models or human subjects.…”

Antidiabetic potential of saffron and its active constituents

“…Finally, the evidence links caspases with β-cell destruction and islet failure(Liadis et al, 2005). Caspases are a family of proteins involved in various forms of cellular death, such asT A B L E 2 Hypoglycemic effects of saffron ingredients by improvement of insulin signaling via phosphorylation of AMPK/ACC; induction of the GLUT4/AMPK molecular pathway, downregulation of adiponectin and TNF-α, lowering of free fatty acids and triglycerides and improvement in the plasma lipid profile, prevention of oxidative stress, inhibition of PTP1B Dehghan et al (2016), Hazman et al (2016), Kang et al (2012), Xi et al (2005), Xi, Qian, Xu, Zheng, et al (2007), Xi, Qian, Xu, Zho, et al (2007), and Yaribeygi, Katsiki, et al (2018) Improvement in β-cell function Prevention of β-cell damage by inhibition of injurious pathways such as oxidative stress and inflammation, suppression of caspase-dependent β-cell damage, downregulation of p53 that is involved in β-cell apoptosis Brownlee (2003), Elgazar et al (2013), Elsherbiny et al (2016), Ghorbanzadeh et al (2017), Keane et al (2015), Liadis et al (2005), Lv et al (2016), and Zhang et al (2015)Induction of GLUT4 expression/localizationInduction of GLUT4 translocation into the plasma membrane by AMPK/ACC and Akt kinase pathways as well as by insulin secretionDu et al (2018),Hazman et al (2016),Maeda et al (2014),Shirali et al (2013),and Yaribeygi, Katsiki, et al (2018) Prevention of oxidative stress Protection against oxidative stress-induced diabetes by potentiation of antioxidant elements and free radical scavengingHatziagapiou and Lambrou (2018),Hu et al (2018),Kianbakht and Hajiaghaee (2011), Maritim et al (2003),Yang et al (2017),Yaribeygi, Faghihi, et al (2018),…”