Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle

2013 ◽  
Vol 455 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Yang Liu ◽  
Yu-Chiang Lai ◽  
Elaine V. Hill ◽  
Donatienne Tyteca ◽  
Sarah Carpentier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Ampk Activation ◽  
Glut4 Translocation ◽  
Skeletal Muscle Glucose Uptake ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

We propose that PIKfyve activity is required for the stimulation of skeletal muscle glucose uptake by contraction/AMPK activation. AMPK-induced phosphorylation of PIKfyve at Ser307 could favour its translocation to endosomes for PtdIns(3,5)P2 production, which facilitates GLUT4 translocation.

scholarly journals Insulin-independent stimulation of skeletal muscle glucose uptake by low-dose abscisic acid via AMPK activation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mirko Magnone ◽  
Laura Emionite ◽  
Lucrezia Guida ◽  
Tiziana Vigliarolo ◽  
Laura Sturla ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Abscisic Acid ◽  
Glucose Uptake ◽  
Low Dose ◽  
Ampk Activation ◽  
Skeletal Muscle Glucose Uptake ◽  
Stimulation Of

scholarly journals Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway

2008 ◽  
Vol 294 (5) ◽  
pp. E889-E897 ◽  
Author(s):  
Yasuki Higaki ◽  
Toshio Mikami ◽  
Nobuharu Fujii ◽  
Michael F. Hirshman ◽  
Katsuhiro Koyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Maximal Increase ◽  
Skeletal Muscle Glucose Uptake ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Phosphatidylinositol 3

We determined the acute effects of oxidative stress on glucose uptake and intracellular signaling in skeletal muscle by incubating muscles with reactive oxygen species (ROS). Xanthine oxidase (XO) is a superoxide-generating enzyme that increases ROS. Exposure of isolated rat extensor digitorum longus (EDL) muscles to Hx/XO (Hx/XO) for 20 min resulted in a dose-dependent increase in glucose uptake. To determine whether the mechanism leading to Hx/XO-stimulated glucose uptake is associated with the production of H2O2, EDL muscles from rats were preincubated with the H2O2 scavenger catalase or the superoxide scavenger superoxide dismutase (SOD) prior to incubation with Hx/XO. Catalase treatment, but not SOD, completely inhibited the increase in Hx/XO-stimulated 2-deoxyglucose (2-DG) uptake, suggesting that H2O2 is an intermediary leading to Hx/XO-stimulated glucose uptake with incubation. Direct H2O2 also resulted in a dose-dependent increase in 2-DG uptake in isolated EDL muscles, and the maximal increase was threefold over basal levels at a concentration of 600 μmol/l H2O2. H2O2-stimulated 2-DG uptake was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, but not the nitric oxide inhibitor N G-monomethyl-l-arginine. H2O2 stimulated the phosphorylation of Akt Ser473 (7-fold) and Thr308 (2-fold) in isolated EDL muscles. H2O2 at 600 μmol/l had no effect on ATP concentrations and did not increase the activities of either the α1 or α2 catalytic isoforms of AMP-activated protein kinase. These results demonstrate that acute exposure of muscle to ROS is a potent stimulator of skeletal muscle glucose uptake and that this occurs through a PI3K-dependent mechanism.

The α-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro

2008 ◽  
Vol 295 (6) ◽  
pp. E1447-E1454 ◽  
Author(s):  
Natalie Lefort ◽  
Emmanuelle St.-Amand ◽  
Sébastien Morasse ◽  
Claude H. Côté ◽  
André Marette
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Force Production ◽  
Force Frequency ◽  
Ampk Activation ◽  
Α Subunit ◽  
Submaximal Contraction ◽  
Fold Stimulation ◽  
Stimulation Of

AMP-activated protein kinase (AMPK) is a key signaling protein in the regulation of skeletal muscle glucose uptake, but its role in mediating contraction-induced glucose transport is still debated. The effect of contraction on glucose transport is impaired in EDL muscle of transgenic mice expressing a kinase-dead, dominant negative form of the AMPKα2 subunit (KD-AMPKα2 mice). However, maximal force production is reduced in this muscle, raising the possibility that the defect in glucose transport was due to a secondary decrease in force production and not impaired AMPKα2 activity. Generation of force-frequency curves revealed that muscle force production is matched between wild-type (WT) and KD-AMPKα2 mice at frequencies ≤50 Hz. Moreover, AMPK activation is already maximal at 50 Hz in muscles of WT mice. When EDL muscles from WT mice were stimulated at a frequency of 50 Hz for 2 min (200-ms train, 1/s, 30 volts), contraction caused an ∼3.5-fold activation of AMPKα2 activity and an ∼2-fold stimulation of glucose uptake. Conversely, whereas force production was similar in EDL of KD-AMPKα2 animals, no effect of contraction was observed on AMPKα2 activity, and glucose uptake stimulation was reduced by 50% ( P < 0.01) As expected, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (AICAR) caused a 2.3-fold stimulation of AMPKα2 activity and a 1.7-fold increase in glucose uptake in EDL from WT mice, whereas no effect was detected in muscle from KD-AMPKα2 mice. These data demonstrate that AMPK activation is essential for both AICAR and submaximal contraction-induced glucose transport in skeletal muscle but that AMPK-independent mechanisms are also involved.

Regulation of glucose transporters by insulin and extracellular glucose in C2C12 myotubes

2006 ◽  
Vol 291 (4) ◽  
pp. E817-E828 ◽  
Author(s):  
Taku Nedachi ◽  
Makoto Kanzaki
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
C2c12 Myotubes ◽  
Glut4 Translocation ◽  
Insulin Stimulation ◽  
Extracellular Glucose ◽  
Insulin Dependent ◽  
Stimulation Of

It is well established that insulin stimulation of glucose uptake in skeletal muscle cells is mediated through translocation of GLUT4 from intracellular storage sites to the cell surface. However, the established skeletal muscle cell lines, with the exception of L6 myocytes, reportedly show minimal insulin-dependent glucose uptake and GLUT4 translocation. Using C2C12 myocytes expressing exofacial-Myc-GLUT4-enhanced cyan fluorescent protein, we herein show that differentiated C2C12 myotubes are equipped with basic GLUT4 translocation machinery that can be activated by insulin stimulation (∼3-fold increase as assessed by anti-Myc antibody uptake and immunostaining assay). However, this insulin stimulation of GLUT4 translocation was difficult to demonstrate with a conventional 2-deoxyglucose uptake assay because of markedly elevated basal glucose uptake via other glucose transporter(s). Intriguingly, the basal glucose transport activity in C2C12 myotubes appeared to be acutely suppressed within 5 min by preincubation with a pathophysiologically high level of extracellular glucose (25 mM). In contrast, this activity was augmented by acute glucose deprivation via an unidentified mechanism that is independent of GLUT4 translocation but is dependent on phosphatidylinositol 3-kinase activity. Taken together, these findings indicate that regulation of the facilitative glucose transport system in differentiated C2C12 myotubes can be achieved through surprisingly acute glucose-dependent modulation of the activity of glucose transporter(s), which apparently contributes to obscuring the insulin augmentation of glucose uptake elicited by GLUT4 translocation. We herein also describe several methods of monitoring insulin-dependent glucose uptake in C2C12 myotubes and propose this cell line to be a useful model for analyzing GLUT4 translocation in skeletal muscle.

scholarly journals Insulin and Leptin Induce Glut4 Plasma Membrane Translocation and Glucose Uptake in a Human Neuronal Cell Line by a Phosphatidylinositol 3-Kinase- Dependent Mechanism

Endocrinology ◽  
2006 ◽  
Vol 147 (5) ◽  
pp. 2550-2556 ◽  
Author(s):  
Yacir Benomar ◽  
Nadia Naour ◽  
Alain Aubourg ◽  
Virginie Bailleux ◽  
Arieh Gertler ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Glut4 Translocation ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Neuronal Cell ◽  
The Impact ◽  
Dependent Mechanism ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

The insulin-sensitive glucose transporter Glut4 is expressed in brain areas that regulate energy homeostasis and body adiposity. In contrast with peripheral tissues, however, the impact of insulin on Glut4 plasma membrane (PM) translocation in neurons is not known. In this study, we examined the role of two anorexic hormones (leptin and insulin) on Glut4 translocation in a human neuronal cell line that express endogenous insulin and leptin receptors. We show that insulin and leptin both induce Glut4 translocation to the PM of neuronal cells and activate glucose uptake. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, totally abolished insulin- and leptin-dependent Glut4 translocation and stimulation of glucose uptake. Thus, Glut4 translocation is a phosphatidylinositol 3-kinase-dependent mechanism in neuronal cells. Next, we investigated the impact of chronic insulin and leptin treatments on Glut4 expression and translocation. Chronic exposure of neuronal cells to insulin or leptin down-regulates Glut4 proteins and mRNA levels and abolishes the acute stimulation of glucose uptake in response to acute insulin or leptin. In addition, chronic treatment with either insulin or leptin impaired Glut4 translocation. A cross-desensitization between insulin and leptin was apparent, where exposure to insulin affects leptin-dependent Glut4 translocation and vice versa. This cross-desensitization could be attributed to the increase in suppressor of cytokine signaling-3 expression, which was demonstrated in response to each hormone. These results provide evidence to suggest that Glut4 translocation to neuronal PM is regulated by both insulin and leptin signaling pathways. These pathways might contribute to an in vivo glucoregulatory reflex involving a neuronal network and to the anorectic effect of insulin and leptin.

scholarly journals Molecular Review: Effects of Physical Exercise in Skeletal Muscle Glucose Uptake

2021 ◽  
Vol 4 (1) ◽  
pp. 1-9
Author(s):  
Rahmi Rahmi
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Glut4 Translocation ◽  
Intracellular Ca ◽  
Skeletal Muscle Glucose Uptake ◽  
T Tubules ◽  
Through Diffusion ◽  
Molecular Signals

Muscle contraction requires glucose as its main fuel. Glucose enters the muscle cells through diffusion facilitated by GLUT4. GLUT4 must be translocated from intracellular to the plasma membrane and T tubules during muscle contraction. This literature review will discuss how physical exercise can signal GLUT4 translocation for glucose uptake. Molecular signals induced by physical exercise are very complex and involve various molecules, one of which is AMPK and intracellular Ca concentration.

scholarly journals β-Sitosterol-D-Glucopyranoside Mimics Estrogenic Properties and Stimulates Glucose Utilization in Skeletal Muscle Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3129
Author(s):  
Jyotsana Pandey ◽  
Kapil Dev ◽  
Sourav Chattopadhyay ◽  
Sleman Kadan ◽  
Tanuj Sharma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Utilization ◽  
Diabetes Management ◽  
Expression System ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cell Periphery ◽  
Glut4 Translocation ◽  
In Silico Docking

Estrogenic molecules have been reported to regulate glucose homeostasis and may be beneficial for diabetes management. Here, we investigated the estrogenic effect of β-sitosterol-3-O-D-glucopyranoside (BSD), isolated from the fruits of Cupressus sempervirens and monitored its ability to regulate glucose utilization in skeletal muscle cells. BSD stimulated ERE-mediated luciferase activity in both ERα and ERβ-ERE luc expression system with greater response through ERβ in HEK-293T cells, and induced the expression of estrogen-regulated genes in estrogen responsive MCF-7 cells. In silico docking and molecular interaction studies revealed the affinity and interaction of BSD with ERβ through hydrophobic interaction and hydrogen bond pairing. Furthermore, prolonged exposure of L6-GLUT4myc myotubes to BSD raised the glucose uptake under basal conditions without affecting the insulin-stimulated glucose uptake, the effect associated with enhanced translocation of GLUT4 to the cell periphery. The BSD-mediated biological response to increase GLUT4 translocation was obliterated by PI-3-K inhibitor wortmannin, and BSD significantly increased the phosphorylation of AKT (Ser-473). Moreover, BSD-induced GLUT4 translocation was prevented in the presence of fulvestrant. Our findings reveal the estrogenic activity of BSD to stimulate glucose utilization in skeletal muscle cells via PI-3K/AKT-dependent mechanism.

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