scholarly journals Fish Glucose Transporter (GLUT)-4 Differs from Rat GLUT4 in Its Traffic Characteristics but Can Translocate to the Cell Surface in Response to Insulin in Skeletal Muscle Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5248-5257 ◽  
Author(s):  
Mònica Díaz ◽  
Costin N. Antonescu ◽  
Encarnación Capilla ◽  
Amira Klip ◽  
Josep V. Planas
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Brown Trout ◽  
Glucose Transporter ◽  
Intracellular Localization ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut 4

In mammals, glucose transporter (GLUT)-4 plays an important role in glucose homeostasis mediating insulin action to increase glucose uptake in insulin-responsive tissues. In the basal state, GLUT4 is located in intracellular compartments and upon insulin stimulation is recruited to the plasma membrane, allowing glucose entry into the cell. Compared with mammals, fish are less efficient restoring plasma glucose after dietary or exogenous glucose administration. Recently our group cloned a GLUT4-homolog in skeletal muscle from brown trout (btGLUT4) that differs in protein motifs believed to be important for endocytosis and sorting of mammalian GLUT4. To study the traffic of btGLUT4, we generated a stable L6 muscle cell line overexpressing myc-tagged btGLUT4 (btGLUT4myc). Insulin stimulated btGLUT4myc recruitment to the cell surface, although to a lesser extent than rat-GLUT4myc, and enhanced glucose uptake. Interestingly, btGLUT4myc showed a higher steady-state level at the cell surface under basal conditions than rat-GLUT4myc due to a higher rate of recycling of btGLUT4myc and not to a slower endocytic rate, compared with rat-GLUT4myc. Furthermore, unlike rat-GLUT4myc, btGLUT4myc had a diffuse distribution throughout the cytoplasm of L6 myoblasts. In primary brown trout skeletal muscle cells, insulin also promoted the translocation of endogenous btGLUT4 to the plasma membrane and enhanced glucose transport. Moreover, btGLUT4 exhibited a diffuse intracellular localization in unstimulated trout myocytes. Our data suggest that btGLUT4 is subjected to a different intracellular traffic from rat-GLUT4 and may explain the relative glucose intolerance observed in fish.

scholarly journals The exocyst complex regulates insulin-stimulated glucose uptake of skeletal muscle cells

2019 ◽  
Vol 317 (6) ◽  
pp. E957-E972
Author(s):  
Brent A. Fujimoto ◽  
Madison Young ◽  
Lamar Carter ◽  
Alina P. S. Pang ◽  
Michael J. Corley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cell Surface Receptor ◽  
Exocyst Complex

Skeletal muscle handles ~80–90% of the insulin-induced glucose uptake. In skeletal muscle, insulin binding to its cell surface receptor triggers redistribution of intracellular glucose transporter GLUT4 protein to the cell surface, enabling facilitated glucose uptake. In adipocytes, the eight-protein exocyst complex is an indispensable constituent in insulin-induced glucose uptake, as it is responsible for the targeted trafficking and plasma membrane-delivery of GLUT4. However, the role of the exocyst in skeletal muscle glucose uptake has never been investigated. Here we demonstrate that the exocyst is a necessary factor in insulin-induced glucose uptake in skeletal muscle cells as well. The exocyst complex colocalizes with GLUT4 storage vesicles in L6-GLUT4myc myoblasts at a basal state and associates with these vesicles during their translocation to the plasma membrane after insulin signaling. Moreover, we show that the exocyst inhibitor endosidin-2 and a heterozygous knockout of Exoc5 in skeletal myoblast cells both lead to impaired GLUT4 trafficking to the plasma membrane and hinder glucose uptake in response to an insulin stimulus. Our research is the first to establish that the exocyst complex regulates insulin-induced GLUT4 exocytosis and glucose metabolism in muscle cells. A deeper knowledge of the role of the exocyst complex in skeletal muscle tissue may help our understanding of insulin resistance in type 2 diabetes.

ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells

2021 ◽  
Author(s):  
Hye Kyoung Sung ◽  
Patricia L. Mitchell ◽  
Sean Gross ◽  
Andre Marette ◽  
Gary Sweeney
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Temporal Analysis ◽  
Skeletal Muscle Cells ◽  
Adiponectin Receptor ◽  
Metabolic Effects

Adiponectin is well established to mediate many beneficial metabolic effects, and this has stimulated great interest in development and validation of adiponectin receptor agonists as pharmaceutical tools. This study investigated the effects of ALY688, a peptide-based adiponectin receptor agonist, in rat L6 skeletal muscle cells. ALY688 significantly increased phosphorylation of several adiponectin downstream effectors, including AMPK, ACC and p38MAPK, assessed by immunoblotting and immunofluorescence microscopy. Temporal analysis using cells expressing an Akt biosensor demonstrated that ALY688 enhanced insulin sensitivity. This effect was associated with increased insulin-stimulated Akt and IRS-1 phosphorylation. The functional metabolic significance of these signaling effects was examined by measuring glucose uptake in myoblasts stably overexpressing the glucose transporter GLUT4. ALY688 treatment both increased glucose uptake itself and enhanced insulin-stimulated glucose uptake. In the model of high glucose/high insulin (HGHI)-induced insulin resistant cells, both temporal studies using the Akt biosensor as well as immunoblotting assessing Akt and IRS-1 phosphorylation indicated that ALY688 significantly reduced insulin resistance. Importantly, we observed that ALY688 administration to high-fat high sucrose fed mice also improve glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects.

scholarly journals Hypoglycemic activity of Phaseolus vulgaris (L.) aqueous extract in type 1 diabetic rats

2019 ◽  
Vol 32 (4) ◽  
pp. 210-218
Author(s):  
Tetiana Halenova ◽  
Natalia Raksha ◽  
Olha Kravchenko ◽  
Tetiana Vovk ◽  
Alona Yurchenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Phaseolus Vulgaris ◽  
Aqueous Extract ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Muscle Cells ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
Skeletal Muscle Cells ◽  
Glut 4

Abstract The aim of the present study was to evaluate the hypoglycemic activity of the aqueous extract from the fruit walls of Phaseolus vulgaris pods and to examine the potential mechanism underlying the improvement of the glycemic level. In the course of the study, diabetes mellitus was induced in rats with a single intraperitoneal injection of streptozotocin (45 mg·kg−1 b.w.). Diabetic and control rats were then orally administered with a single-dose or repeated-dose (28 day) of P. vulgaris extract (200 mg·kg−1). Results show that the extract was found to possess significant hypoglycemic activity, and the study of glucose utilization by isolated rat hemidiaphragm suggests that the aqueous extract may enhance the peripheral utilization of glucose. The subsequent experiments have revealed that the P. vulgaris extract could increase glucose transporter 4 (GLUT-4) content in skeletal muscle cells of control and diabetic rats. Our data also indicate that the P. vulgaris extract did not affect the content of the insulin receptor, but significantly reduced the total tyrosine kinase activity in skeletal muscle cells of both experimental groups of rats. The present results clearly indicated that P. vulgaris extract may be beneficial for reducing hyperglycemia through its potency in regulation of glucose utilization via GLUT-4, but the current mechanism remains to be unidentified.

scholarly journals The effects of muscle contraction and insulin on glucose-transporter translocation in rat skeletal muscle

1994 ◽  
Vol 297 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J T Brozinick ◽  
G J Etgen ◽  
B B Yaspelkis ◽  
J L Ivy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Protein Distribution ◽  
Sprague Dawley ◽  
Glut 4

The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.

scholarly journals Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells

2021 ◽  
Vol 26 ◽  
pp. 2515690X2110063
Author(s):  
F. D. Y. Kamga-Simo ◽  
G. P. Kamatou ◽  
C. Ssemakalu ◽  
L. J. Shai
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Glucose Absorption ◽  
Skeletal Muscle Cells ◽  
Bark Extract ◽  
Aqueous Extracts ◽  
Glut 4 ◽  
Glut 4 Translocation

Background. This study aim at assessing C. abbreviata aqueous extracts for its potential to exhibit anti-diabetic activity in skeletal muscle cells. In addition to the toxicological and glucose absorption studies, the action of C. abbreviata extracts on some major genes involved in the insulin signaling pathway was established. Methods. The in vitro cytotoxic effects C. abbreviata was evaluated on muscle cells using the MTT assay and the in vitro glucose uptake assay conducted using a modified glucose oxidase method described by Van de Venter et al. (2008). The amount of GLUT-4 on cell surfaces was estimated quantitatively using the flow cytometry technique. Real time quantitative PCR (RT-qPCR) was used to determine the expression of GLUT-4, IRS-1, PI3 K, Akt1, Akt2, PPAR-γ. Results. Cytotoxicity tests revealed that all extracts tested at various concentrations were non-toxic (LC50 > 5000). Aqueous extracts of leaves, bark and seeds resulted in a dose-dependent increase in glucose absorption by cells, after 1 h, 3 h and 6 h incubation period. Extracts of all three plant parts had the best effect after 3 h incubation, with the leaf extract showing the best activity across time (Glucose uptake of 29%, 56% and 42% higher than untreated control cells after treatment with 1 mg/ml extract at 1 h, 3 h and 6 h, respectively). All extracts, with the exception 500 µg/ml seed extract, induced a two-fold increase in GLUT-4 translocation while marginally inducing GLUT-10 translocation in the muscle cells. The indirect immunofluorescence confirmed that GLUT-4 translocation indeed occurred. There was an increased expression of GLUT-4, IRS1 and PI3 K in cells treated with insulin and bark extract as determined by the RT-qPCR. Conclusion. The study reveals that glucose uptake involves GLUT-4 translocation through a mechanism that is likely to involve the upstream effectors of the PI3-K/Akt pathway.

Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle

2008 ◽  
Vol 294 (5) ◽  
pp. E961-E968 ◽  
Author(s):  
Koji Sato ◽  
Motoyuki Iemitsu ◽  
Katsuji Aizawa ◽  
Ryuichi Ajisaka
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut 4 ◽  
Kinase C ◽  
Pkc Ζ

Circulating dehydroepiandrosterone (DHEA) is converted to testosterone or estrogen in the target tissues. Recently, we demonstrated that skeletal muscles are capable of locally synthesizing circulating DHEA to testosterone and estrogen. Furthermore, testosterone is converted to 5α-dihydrotestosterone (DHT) by 5α-reductase and exerts biophysiological actions through binding to androgen receptors. However, it remains unclear whether skeletal muscle can synthesize DHT from testosterone and/or DHEA and whether these hormones affect glucose metabolism-related signaling pathway in skeletal muscles. We hypothesized that locally synthesized DHT from testosterone and/or DHEA activates glucose transporter-4 (GLUT-4)-regulating pathway in skeletal muscles. The aim of the present study was to clarify whether DHT is synthesized from testosterone and/or DHEA in cultured skeletal muscle cells and whether these hormones affect the GLUT-4-related signaling pathway in skeletal muscles. In the present study, the expression of 5α-reductase mRNA was detected in rat cultured skeletal muscle cells, and the addition of testosterone or DHEA increased intramuscular DHT concentrations. Addition of testosterone or DHEA increased GLUT-4 protein expression and its translocation. Furthermore, Akt and protein kinase C-ζ/λ (PKC-ζ/λ) phosphorylations, which are critical in GLUT-4-regulated signaling pathways, were enhanced by testosterone or DHEA addition. Testosterone- and DHEA-induced increases in both GLUT-4 expression and Akt and PKC-ζ/λ phosphorylations were blocked by a DHT inhibitor. Finally, the activities of phosphofructokinase and hexokinase, main glycolytic enzymes, were enhanced by testosterone or DHEA addition. These findings suggest that skeletal muscle is capable of synthesizing DHT from testosterone, and that DHT activates the glucose metabolism-related signaling pathway in skeletal muscle cells.

Glucose uptake stimulatory effect of 4-hydroxypipecolic acid by increased GLUT 4 translocation in skeletal muscle cells

2012 ◽  
Vol 22 (17) ◽  
pp. 5648-5651 ◽  
Author(s):  
G. Naresh ◽  
N. Jaiswal ◽  
P. Sukanya ◽  
A.K. Srivastava ◽  
A.K. Tamrakar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut 4 ◽  
Glut 4 Translocation
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