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.

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.

Prenylated chalcones 4-hydroxyderricin and xanthoangelol stimulate glucose uptake in skeletal muscle cells by inducing GLUT4 translocation

2010 ◽  
Vol 55 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Kyuichi Kawabata ◽  
Keisuke Sawada ◽  
Kazunori Ikeda ◽  
Itsuko Fukuda ◽  
Kengo Kawasaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation ◽  
Prenylated Chalcones

scholarly journals Electrical Stimuli Release ATP to Increase GLUT4 Translocation and Glucose Uptake via PI3K -Akt-AS160 in Skeletal Muscle Cells

Diabetes ◽  
2012 ◽  
Vol 62 (5) ◽  
pp. 1519-1526 ◽  
Author(s):  
C. Osorio-Fuentealba ◽  
A. E. Contreras-Ferrat ◽  
F. Altamirano ◽  
A. Espinosa ◽  
Q. Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation ◽  
Electrical Stimuli

scholarly journals Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells

2006 ◽  
Vol 399 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Nikolaos Dimopoulos ◽  
Maria Watson ◽  
Kei Sakamoto ◽  
Harinder S. Hundal
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Insulin Signalling ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
L6 Skeletal Muscle Cells

An increase in circulating levels of specific NEFAs (non-esterified fatty acids) has been implicated in the pathogenesis of insulin resistance and impaired glucose disposal in skeletal muscle. In particular, elevation of SFAs (saturated fatty acids), such as palmitate, has been correlated with reduced insulin sensitivity, whereas an increase in certain MUFAs and PUFAs (mono- and poly-unsaturated fatty acids respectively) has been suggested to improve glycaemic control, although the underlying mechanisms remain unclear. In the present study, we compare the effects of palmitoleate (a MUFA) and palmitate (a SFA) on insulin action and glucose utilization in rat L6 skeletal muscle cells. Basal glucose uptake was enhanced approx. 2-fold following treatment of cells with palmitoleate. The MUFA-induced increase in glucose transport led to an associated rise in glucose oxidation and glycogen synthesis, which could not be attributed to activation of signalling proteins normally modulated by stimuli such as insulin, nutrients or cell stress. Moreover, although the MUFA-induced increase in glucose uptake was slow in onset, it was not dependent upon protein synthesis, but did, nevertheless, involve an increase in the plasma membrane abundance of GLUT1 and GLUT4. In contrast, palmitate caused a substantial reduction in insulin signalling and insulin-stimulated glucose transport, but was unable to antagonize the increase in transport elicited by palmitoleate. Our findings indicate that SFAs and MUFAs exert distinct effects upon insulin signalling and glucose uptake in L6 muscle cells and suggest that a diet enriched with MUFAs may facilitate uptake and utilization of glucose in normal and insulin-resistant skeletal muscle.

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
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