Regulation of glucose transporters by insulin and extracellular glucose in C<sub>2</sub>C<sub>12</sub>myotubes

Nedachi, Taku; Kanzaki, Makoto

doi:10.1152/ajpendo.00194.2006

Cited by 87 publications

(99 citation statements)

References 64 publications

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“…We quantified differentiation status by counting the number of myotubes defined as multinuclear myotubes that contained more than 5 nuclei (Fig. 1B), as we previously reported (37). The effect of the extracellular glucose concentration on myogenesis was confirmed by Western blot analysis of differentiation marker proteins using anti-skeletal muscle type MHC and anti-myogenin antibodies, as not only were their expressions detected later, but their amounts were also lower than in C 2 C 12 cells differentiated under LG conditions (Fig.…”

Section: Extracellular Glucose Influences Lowmentioning

confidence: 99%

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Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes

Nedachi

Kadotani²,

Ariga³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Nedachi T, Kadotani A, Ariga M, Katagiri H, Kanzaki M. Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C 2C12 myocytes. Am J Physiol Endocrinol Metab 294: E668-E678, 2008. First published January 29, 2008 doi:10.1152/ajpendo.00640.2007.-Nutrition availability is one of the major environmental signals influencing cell fate, such as proliferation, differentiation, and apoptosis, often functioning in concert with other humoral factors, including insulin. Herein, we show that low-serum-induced differentiation of C 2C12 myocytes is significantly hampered under low glucose (LG; 5 mM) compared with high glucose (HG; 22.5 mM) conditions, concurrently with nuclear accumulation of SIRT1, an NAD ϩ -dependent deacetylase, and FoxO3a, both of which are implicated in the negative regulation of myogenesis. Intriguingly, insulin appears to exert opposite actions, depending on glucose availability, with regard to the regulation of SIRT1 and FoxO3a abundance, which apparently contributes to modulating the potency of insulin's myogenic action. Namely, insulin exerts a potent myogenic effect in the presence of sufficient glucose, whereas insulin is unable to exert its myogenic action under LG conditions, since insulin evokes massive upregulation of both SIRT1 and FoxO3a in the absence of sufficient ambient glucose. In addition, the hampered differentiation state under LG is significantly restored by sirtinol, a SIRT1 inhibitor, whereas insulin abolished this sirtinoldependent restoration, indicating that insulin can function as a negative as well as a positive myogenic factor depending on glucose availability. Taken together, our data reveal the importance of ambient glucose levels in the regulation of myogenesis and also in the determination of insulin's myogenic potency, which is achieved, at least in part, through regulation of the cellular contents and localization of SIRT1 and FoxO3a in differentiating C 2C12 myocytes.forkhead box O; differentiation SKELETAL MUSCLE CELLS have provided a useful model for exploring the molecular mechanisms involved in cellular differentiation (13), and insulin and insulin-like growth factors (IGFs) have been implicated in the process of myogenesis by activating the IRS-PI 3-kinase signaling pathway (7,22,25,53) that also serves as a pivotal intracellular signal for exerting metabolic actions in mature skeletal muscle (9). However, despite our general understanding of the effects of ambient glucose levels on insulin responsiveness with regard to metabolic actions in skeletal muscle cells (37), the possible interrelationship between glucose and insulin acting on myogenesis remains to be clarified.Skeletal muscle differentiation is a well-organized process governed by muscle-specific transcription factors belonging to the MyoD family, such as MyoD and myogenin (42), and the myocyte enhancer factor-2 (MEF2) family, such as MEF2A and MEF2C (35). In addition to these muscle-specific transcription factors, positively regulating myogenesis, the f...

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Section: Extracellular Glucose Influences Lowmentioning

confidence: 99%

“…However, despite our general understanding of the effects of ambient glucose levels on insulin responsiveness with regard to metabolic actions in skeletal muscle cells (37), the possible interrelationship between glucose and insulin acting on myogenesis remains to be clarified.…”

mentioning

confidence: 99%

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes

Nedachi

Kadotani²,

Ariga³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…Other studies have shown GLUT4 enhancement under different concentrations of cinnamon extract or dihydrocinnamic acid (DHH105), a derivative of cinnamon, on GLUT4 content in animal adipose tissue [17] or 3T3-L1 cell line, a good model for studding fat tissue metabolism [14]. But muscular tissue is the most important site for glucose metabolism which uses more than 75 % of body glucose expenditure under insulin impact [18][19][20][21]. As the rate limiting step of blood glucose level expenditure is regulated by GLUT4 glycoprotein presence in the cytoplasmic membrane [22,23], the objective of current study was to investigate the effect of cinnamon water extract on GLUT4 contents of cytoplasmic membrane (CM) and nuclear/endoplasmic (N/ER) reticulum fractions of differentiated C2C12 myotubes.…”

Section: Introductionmentioning

confidence: 99%

Hydro-Alcoholic Cinnamon Extract, Enhances Glucose Transporter Isotype-4 Translocation from Intracellular Compartments into the Cytoplasmic Membrane of C2C12 Myotubes

et al. 2012

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Cinnamon has been used as an anti-diabetic agent for centuries but only in recent few years its mechanism of action has been under investigation. Previous studies showed that cinnamon might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in fat cells. To study if hydro-alcoholic cinnamon extract (HACE) enhances GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 100 or 1,000 lg/ml HACE, as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two-independent samples t test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM of groups 100 and 1,000 lg/ml HACE and lower in 1 % DMSO treated myotubes (CI = 0.95, P \ 0.05). For N/ER reverse results were obtained (CI = 0.95, P \ 0.05). As our results have shown HACE induces GLUT4 translocation from intra-cell into cell surface. We conclude that cinnamon maybe a choice of type-2 diabetes mellitus treatment because its extract enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However it is necessary to trace the signaling pathways which are activated by HACE in muscular tissue.

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“…Attempts have been made to develop efficient in vitro model systems for in-depth studies on the glucose uptake involving GLUT4 in muscle cells. However, such systems have been still awaited, since most of the established skeletal muscle cell lines reportedly show minimal insulin-dependent glucose uptake and translocation of GLUT4, and only the exceptions are rat L6 and mouse C2C12 myotubes (Nedachi and Kanzaki 2006). When stimulated by insulin, L6 myotubes appeared to exhibit glucose uptake to a larger extent than C2C12 cells (Sarabia et al 1990), suggesting that at present L6 myotubes could be the most promising candidate as an efficient in vitro model system to investigate glucose uptake in muscle cells.…”

Section: Introductionmentioning

confidence: 99%

Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

et al. 2007

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Some of inositol derivatives have been reported to help the action of insulin stimulating glucose uptake in skeletal muscle cells. Rat L6 myotubes were employed in an attempt to develop an in vitro model system for investigation of the possible insulin-like effect of eight inositol derivatives, namely allo-inositol, D-chiro-inositol L-chiro-inositol, epi-inositol, muco-inositol, myo-inositol, scyllo-inositol and D-pinitol. At a higher concentration of 1 mM seven inositol derivatives other than myo-inositol were able to stimulate glucose uptake, while at 0.1 mM only D-chiro-inositol, L-chiro-inositol, epiinositol and muco-inositol could induce glucose uptake, indicating their significant insulin-mimetic activity. Immunoblot analyses revealed that at least Dchiro-inositol, L-chiro-inositol, epi-inositol, mucoinositol and D-pinitol were able to induce translocation of glucose transporter 4 (GLUT4) to plasma membrane not only in L6 myotubes but also in skeletal muscles of rats ex vivo. These results demonstrated that L6 myotubes appeared efficient as an in vitro system to identify inositol derivatives exerting an insulin-like effect on muscle cells depending on the induced translocation of GLUT4.

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Regulation of glucose transporters by insulin and extracellular glucose in C₂C₁₂myotubes

Abstract: Nedachi, Taku, and Makoto Kanzaki. Regulation of glucose transporters by insulin and extracellular glucose in C2C12 myotubes.

Cited by 87 publications

References 64 publications

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes

Hydro-Alcoholic Cinnamon Extract, Enhances Glucose Transporter Isotype-4 Translocation from Intracellular Compartments into the Cytoplasmic Membrane of C2C12 Myotubes

Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

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Regulation of glucose transporters by insulin and extracellular glucose in C2C12myotubes

Abstract: Nedachi, Taku, and Makoto Kanzaki. Regulation of glucose transporters by insulin and extracellular glucose in C2C12 myotubes.

Cited by 87 publications

References 64 publications

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C2C12 myocytes

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C2C12 myocytes

Hydro-Alcoholic Cinnamon Extract, Enhances Glucose Transporter Isotype-4 Translocation from Intracellular Compartments into the Cytoplasmic Membrane of C2C12 Myotubes

Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

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Regulation of glucose transporters by insulin and extracellular glucose in C₂C₁₂myotubes

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes

Ambient glucose levels qualify the potency of insulin myogenic actions by regulating SIRT1 and FoxO3a in C₂C₁₂ myocytes