scholarly journals Chrysin in Combination with Insulin Promotes Glucose Uptake in Skeletal Muscle Cell: Impact of Combination Therapy in Diabetes Myopathy (P01-031-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Poonam Kalhotra ◽  
Veera Chandra Sekhar Reddy Chittepu ◽  
Guillermo Osorio-Revilla ◽  
Tzayhri Gallardo-Velazquez
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Pathway Analysis ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
P Value ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Funding Sources

Abstract Objectives The objective of the current study was examining the beneficial effects of DPP4 inhibitor chrysin alone and in combination with insulin benefits diabetes myopathy. Methods Sulforhodamine B (SRB) protein-dye was used to determine the acute toxicity, and 1H NMR spectroscopy was used to identify and quantify glucose levels to assess glucose uptake on treatments chrysin and combination of chrysin with Insulin on differentiated skeletal muscle cells. Pathway analysis was carried out using omics net web server. All experiments were conducted in triplicates, and all data in the graph represent Mean ± S.D. Graph pad software was used to calculate One-way analysis of variance (ANOVA), computed p-value among different groups and values with P < 0.05 is significant. Results Results showed that 250 µM chrysin and combination (10 nM Insulin with 250 µM chrysin) treatments are not acutely toxic to skeletal muscle cells and proliferates the cells significant to insulin-treated skeletal muscle cells (Figure 1A). Glucose metabolite levels are studied as skeletal muscle cells adopted cell proliferative and to demonstrate our hypothesis on glucose metabolism. Significant differences were observed in skeletal muscle cells treated with insulin, chrysin, and combination (Figure 1B). It is observed that chrysin alone, combination increases glucose uptake significantly in comparison to control cells. Pathway analysis revealed that GPCR signaling and immune-related signaling plays a role in proliferating skeletal muscle cells to regulate glucose metabolism. Conclusions The results of this study propose the use of natural compound chrysin in combination with insulin to promote skeletal muscle health in diabetes mellitus. The combination identified herein must be considered for future therapies to control diabetic myopathy in preclinical and clinical studies. Chrysin can also be applied as a supplement in the diet as well, to control diabetic myopathy. Funding Sources Authors wish to express their gratitude to Escuela Nacional de Ciencias Biológicas-Instituto Politécnico Nacional (ENCB-IPN) for providing financial support for the present study. Supporting Tables, Images and/or Graphs

scholarly journals Shikonin Increases Glucose Uptake in Skeletal Muscle Cells and Improves Plasma Glucose Levels in Diabetic Goto-Kakizaki Rats

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22510 ◽  
Author(s):  
Anette I. Öberg ◽  
Kamal Yassin ◽  
Robert I. Csikasz ◽  
Nodi Dehvari ◽  
Irina G. Shabalina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glucose Levels

Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells

2014 ◽  
Vol 306 (9) ◽  
pp. E1065-E1076 ◽  
Author(s):  
Hidemitsu Sakagami ◽  
Yuichi Makino ◽  
Katsutoshi Mizumoto ◽  
Tsubasa Isoe ◽  
Yasutaka Takeda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation

Defects in glucose uptake by the skeletal muscle cause diseases linked to metabolic disturbance such as type 2 diabetes. The molecular mechanism determining glucose disposal in the skeletal muscle in response to cellular stimuli including insulin, however, remains largely unknown. The hypoxia-inducible factor-1α (HIF-1α) is a transcription factor operating in the cellular adaptive response to hypoxic conditions. Recent studies have uncovered pleiotropic actions of HIF-1α in the homeostatic response to various cellular stimuli, including insulin under normoxic conditions. Thus we hypothesized HIF-1α is involved in the regulation of glucose metabolism stimulated by insulin in the skeletal muscle. To this end, we generated C2C12myocytes in which HIF-1α is knocked down by short-hairpin RNA and examined the intracellular signaling cascade and glucose uptake subsequent to insulin stimulation. Knockdown of HIF-1α expression in the skeletal muscle cells resulted in abrogation of insulin-stimulated glucose uptake associated with impaired mobilization of glucose transporter 4 (GLUT4) to the plasma membrane. Such defect seemed to be caused by reduced phosphorylation of the protein kinase B substrate of 160 kDa (AS160). AS160 phosphorylation and GLUT4 translocation by AMP-activated protein kinase activation were abrogated as well. In addition, expression of the constitutively active mutant of HIF-1α (CA-HIF-1α) or upregulation of endogenous HIF-1α in C2C12cells shows AS160 phosphorylation comparable to the insulin-stimulated level even in the absence of insulin. Accordingly GLUT4 translocation was increased in the cells expressing CA-HIF1α. Taken together, HIF-1α is a determinant for GLUT4-mediated glucose uptake in the skeletal muscle cells thus as a possible target to alleviate impaired glucose metabolism in, e.g., type 2 diabetes.

scholarly journals Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julie Massart ◽  
Rasmus J. O. Sjögren ◽  
Brendan Egan ◽  
Christian Garde ◽  
Magnus Lindgren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Aerobic Exercise Training ◽  
Human Skeletal Muscle Cells

AbstractSkeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.

scholarly journals Plant-Derived Trans-β-Caryophyllene Boosts Glucose Metabolism and ATP Synthesis in Skeletal Muscle Cells through Cannabinoid Type 2 Receptor Stimulation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 916
Author(s):  
Federica Geddo ◽  
Susanna Antoniotti ◽  
Giulia Querio ◽  
Iris Chiara Salaroglio ◽  
Costanzo Costamagna ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Atp Synthesis ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Whole Body ◽  
Cb2 Receptor ◽  
Receptor Stimulation

Skeletal muscle plays a pivotal role in whole-body glucose metabolism, accounting for the highest percentage of glucose uptake and utilization in healthy subjects. Impairment of these key functions occurs in several conditions including sedentary lifestyle and aging, driving toward hyperglycemia and metabolic chronic diseases. Therefore, strategies pointed to improve metabolic health by targeting skeletal muscle biochemical pathways are extremely attractive. Among them, we focused on the natural sesquiterpene and cannabinoid type 2 (CB2) receptor agonist Trans-β-caryophyllene (BCP) by analyzing its role in enhancing glucose metabolism in skeletal muscle cells. Experiments were performed on C2C12 myotubes. CB2 receptor membrane localization in myotubes was assessed by immunofluorescence. Within glucose metabolism, we evaluated glucose uptake (by the fluorescent glucose analog 2-NBDG), key enzymes of both glycolytic and oxidative pathways (by spectrophotometric assays and metabolic radiolabeling) and ATP production (by chemiluminescence-based assays). In all experiments, CB2 receptor involvement was tested with the CB2 antagonists AM630 and SR144528. Our results show that in myotubes, BCP significantly enhances glucose uptake, glycolytic and oxidative pathways, and ATP synthesis through a CB2-dependent mechanism. Giving these outcomes, CB2 receptor stimulation by BCP could represent an appealing tool to improve skeletal muscle glucose metabolism, both in physiological and pathological conditions.

scholarly journals SUN-657 The Effect of Simvastatin on Glucose Metabolism in Primary Human Muscle Cells

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Selina Mäkinen ◽  
Neeta Datta-Sengupta ◽  
Yen Nguyen ◽  
Petro Kyrylenko ◽  
Markku Laakso ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Form ◽  
Lactone Form ◽  
Human Skeletal Muscle Cells ◽  
Glucose Incorporation

Abstract Statin use, especially treatment with simvastatin, is associated with impaired insulin secretion and whole-body insulin sensitivity, and increased risk for T2D. Here, we investigated the direct effects of lactone- and acid-forms of simvastatin on glucose metabolism in primary human skeletal muscle cells. Exposure of human myotubes to lactone-form simvastatin for 48 h increased glucose uptake and glucose incorporation into glycogen, whereas the acid-form did not affect glucose uptake and decreased glucose incorporation into glycogen. These metabolic actions were accompanied by changes in insulin signaling, as phosphorylation of AS160 and GSK3β was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both lactone and acid-forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. Collectively these data indicate that lactone- and acid forms of simvastatin exhibit differences such that lactone-form increases, and acid-form impairs glucose incorporation into glycogen. Exposure to either form of simvastatin, however, impairs glycolysis and mitochondrial oxidative metabolism in human skeletal muscle cells.

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.

The effect of the nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells

Nitric Oxide ◽  
2009 ◽  
Vol 21 (2) ◽  
pp. 126-131 ◽  
Author(s):  
Darren C. Henstridge ◽  
Brian G. Drew ◽  
Melissa F. Formosa ◽  
Alaina K. Natoli ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Sodium Nitroprusside ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Nitric Oxide Donor

scholarly journals Signaling of the p21-activated kinase (PAK1) coordinates insulin-stimulated actin remodeling and glucose uptake in skeletal muscle cells

2014 ◽  
Vol 92 (2) ◽  
pp. 380-388 ◽  
Author(s):  
Ragadeepthi Tunduguru ◽  
Tim T. Chiu ◽  
Latha Ramalingam ◽  
Jeffrey S. Elmendorf ◽  
Amira Klip ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Actin Remodeling ◽  
P21 Activated Kinase

scholarly journals Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK

2015 ◽  
Vol 29 (6) ◽  
pp. 873-881 ◽  
Author(s):  
Hye Jeong Lee ◽  
Jung Ok Lee ◽  
Nami Kim ◽  
Joong Kwan Kim ◽  
Hyung Ip Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

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.

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