Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4

A methanolic extract from the dried root of Dendrobium christyanum Rchb.f. (Orchidaceae) exhibited α-glucosidase inhibitory activity and glucose uptake stimulatory effect. Chromatographic separation of the extract led to the isolation of 13 phenolic compounds (1-13). Their structures were determined by spectroscopic analysis. The isolates were then evaluated for in vitro α-glucosidase inhibitory and glucose uptake stimulatory activities. Methyl haematommate (1), methyl 2,4-dihydroxy-3,6-dimethylbenzoate (3), n-docosyl 4-hydroxy- trans-cinnamate (4), coniferyl aldehyde (6), 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (7), gigantol (10), and diorcinolic acid (13) showed higher α-glucosidase inhibitory activity than the drug acarbose. Moreover, n-docosyl 4-hydroxyl- trans-cinnamate (4), vanillin (5), and coniferyl aldehyde (6) could enhance glucose uptake by L6 myotubes. Compounds 4 and 6 appear to be potential hypoglycemic agents since they possess both α-glucosidase inhibitory and glucose uptake stimulatory activities. This study is the first report on the chemical constituents and antidiabetic activity of D. christyanum.

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Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates Insulin resistance by upregulating GLUT-4, PPAR- and #947;, adiponectin and leptin levels in vitro

Journal of Intercultural Ethnopharmacology ◽

10.5455/jice.20160224051727 ◽

2016 ◽

Vol 5 (2) ◽

pp. 146 ◽

Cited By ~ 8

Author(s):

Puttanarasaiah Kumar ◽

Marikunte Venkataranganna ◽

Kirangadur Manjunath ◽

Gollapalle Viswanatha ◽

Godavarthi Ashok

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Leaf Extract ◽

Gymnema Sylvestre ◽

Glut 4

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GLUT4 translocation precedes the stimulation of glucose uptake by insulin in muscle cells: potential activation of GLUT4 via p38 mitogen-activated protein kinase

Biochemical Journal ◽

10.1042/bj3590639 ◽

2001 ◽

Vol 359 (3) ◽

pp. 639-649 ◽

Cited By ~ 62

Author(s):

Romel SOMWAR ◽

David Y. KIM ◽

Gary SWEENEY ◽

Carol HUANG ◽

Wenyan NIU ◽

...

Keyword(s):

Protein Kinase ◽

Glucose Uptake ◽

P38 Mapk ◽

Mitogen Activated Protein Kinase ◽

Kinase Assay ◽

Glut4 Translocation ◽

L6 Myotubes ◽

Mitogen Activated Protein ◽

Stimulation Of

We previously reported that SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), attenuates insulin-stimulated glucose uptake without altering GLUT4 translocation. These results suggested that insulin might activate GLUT4 via a p38 MAPK-dependent pathway. Here we explore this hypothesis by temporal and kinetic analyses of the stimulation of GLUT4 translocation, glucose uptake and activation of p38 MAPK isoforms by insulin. In L6 myotubes stably expressing GLUT4 with an exofacial Myc epitope, we found that GLUT4 translocation (t1/2 = 2.5min) preceded the stimulation of 2-deoxyglucose uptake (t1/2 = 6min). This segregation of glucose uptake from GLUT4 translocation became more apparent when the two parameters were measured at 22°C. Preincubation with the p38 MAPK inhibitors SB202190 and SB203580 reduced insulin-stimulated transport of either 2-deoxyglucose or 3-O-methylglucose by 40–60%. Pretreatment with SB203580 lowered the apparent transport Vmax of insulin-mediated 2-deoxyglucose and 3-O-methylglucose without any significant change in the apparent Km for either hexose. The IC50 values for the partial inhibition of 2-deoxyglucose uptake by SB202190 and SB203580 were 1 and 2μM respectively, and correlated with the IC50 for full inhibition of p38 MAPK by the two inhibitors in myotubes (2 and 1.4μM, respectively). Insulin caused a dose- (EC50 = 15nM) and time- (t1/2 = 3min) dependent increase in p38 MAPK phosphorylation, which peaked at 10min (2.3±0.3-fold). In vitro kinase assay of immunoprecipitates from insulin-stimulated myotubes showed activation of p38α (2.6±0.3-fold) and p38β (2.3±0.2-fold) MAPK. These results suggest that activation of GLUT4 follows GLUT4 translocation and that both mechanisms contribute to the full stimulation of glucose uptake by insulin. Furthermore, activation of GLUT4 may occur via an SB203580-sensitive pathway, possibly involving p38 MAPK.

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Enhancement of glucose uptake by Ficus hispida methanolic extract through phosphatidylinositol 3 kinase and inhibiting aldose reductase – An in vitro analysis

European Journal of Integrative Medicine ◽

10.1016/j.eujim.2014.12.004 ◽

2015 ◽

Vol 7 (2) ◽

pp. 164-171 ◽

Cited By ~ 1

Author(s):

Singaravelu Anand ◽

Rajaganapathy Bharathi Raja ◽

Baddireddi Subhadra Lakshmi

Keyword(s):

Glucose Uptake ◽

Aldose Reductase ◽

Methanolic Extract ◽

Phosphatidylinositol 3 Kinase ◽

Ficus Hispida ◽

Vitro Analysis ◽

In Vitro Analysis ◽

Phosphatidylinositol 3

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In vitro free radical scavenging and antidiabetic activity of aqueous and ethanolic leaf extracts: a comparative evaluation of Argyreia pierreana and Matelea denticulata

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-019-0014-9 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 3

Author(s):

Venkataiah Gudise ◽

Bimalendu Chowdhury ◽

Arehalli S. Manjappa

Keyword(s):

Glucose Uptake ◽

Radical Scavenging ◽

Vascular Complications ◽

Total Phenolic ◽

Aqueous Extracts ◽

Leaf Extracts ◽

Glut 4 ◽

Ethanolic Extracts ◽

Phenolic And Flavonoid

Abstract Background Oxidation is believed to play a vital role in the pathogenesis of diabetes mellitus by lipid peroxidation; DNA and protein damage leads to the development of vascular complications like coronary heart disease, stroke, neuropathy, retinopathy, and nephropathy. The herbal preparations are complementary and alternative medicines to allopathic drugs which are believed to cause adverse events. Therefore, the current study was aimed to identify the novel plants, which belong to the genera Argyreia (Argyreia pierreana (AP)) and Matelea (Matelea denticulata (MD)), and assess the aqueous and ethanolic leaf extracts for in vitro antioxidant and antidiabetic potential by DPPH, OH•, superoxide, and glucose uptake and gene expression (GLUT-4 and PPARγ) studies using the L-6 cell line respectively. Results The preliminary scrutiny revealed the presence of polyphenols, flavonoids, terpenoids, steroids, tannins, alkaloids, and glycosides. The total phenolic and flavonoid contents of ethanolic extracts were found higher than those of aqueous extracts. The ethanolic extracts exhibited the superior antioxidant capacity when compared with aqueous extracts. However, the ethanolic extract of MD was shown superlative glucose uptake activity (72.54%) over control (0.037%) and GLUT-4 and PPARγ gene expressions (1.17 and 1.20) in term of folds respectively over cell control (1.00). Conclusion The ethanolic leaf extracts of both plants showed significant in vitro antioxidant and antidiabetic activities compare to aqueous extracts. The Matelea denticulata ethanolic leaf extract exhibited superior activity. This superior activity might be due to their higher phenolic and flavonoid content. However, further approaches are needed to define these activities.

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In vitro and in silico characterization of adiponectin-receptor agonist dipeptides

npj Science of Food ◽

10.1038/s41538-021-00114-2 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Yuna Lee ◽

Akihiro Nakano ◽

Saya Nakamura ◽

Kenta Sakai ◽

Mitsuru Tanaka ◽

...

Keyword(s):

Glucose Uptake ◽

Glucose Transporter ◽

Adenosine Monophosphate ◽

Adiponectin Receptor ◽

L6 Myotubes ◽

Glut4 Expression ◽

Binding Pockets ◽

Dynamics Simulations ◽

In Silico Characterization

AbstractThe aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist.

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The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00162.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. E237-E248 ◽

Cited By ~ 5

Author(s):

Heidy Cabrera-Cruz ◽

Lorena Oróstica ◽

Francisca Plaza-Parrochia ◽

Ignacio Torres-Pinto ◽

Carmen Romero ◽

...

Keyword(s):

Glucose Uptake ◽

In Vitro Model ◽

Normal Weight ◽

Endometrial Cells ◽

Insulin Resistant ◽

Protein Levels ◽

Glut 4 ◽

Vitro Model ◽

Dependent Mechanism

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity ( P < 0.05 vs. normal weight ). In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO ( P < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism ( P < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.

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ANTI-DIABETIC AND ALDOSE REDUCTASE INHIBITORY POTENTIAL OF PSIDIUM GUAJAVA BY IN VITRO ANALYSIS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016.v8i9.13532 ◽

2016 ◽

Vol 8 (9) ◽

pp. 271 ◽

Cited By ~ 4

Author(s):

Singaravelu Anand ◽

Munichetty Arasakumari ◽

Panneervelu Prabu ◽

Arul Joseph Amalraj

Keyword(s):

Glucose Uptake ◽

Aldose Reductase ◽

Inhibitory Activity ◽

Psidium Guajava ◽

Inhibitory Effect ◽

Cellular Level ◽

L6 Myotubes ◽

Successive Extraction ◽

Vitro Analysis

Objective: The objective of the present study was to determine the cellular level effect on glucose uptake and aldose reductase inhibitory activity of different extracts of traditional medicinal plant Psidium guajava.Methods: Psidium guajava was selected and subjected for successive extraction from non-polar to polar solvents and subjected to glucose uptake and aldose reductase inhibition assay.Results: Based on the results Psidium guajava methanolic extract (PGME) showed an enhancement in the glucose uptake and also up-regulates the gene and protein level expression of IRβ, IRS-1, PI3K and GLUT4. Wortmannin, a specific PI3K inhibitor confirms that the active PGME recruits glucose uptake through a PI3K dependent pathway. In the assay of aldose reductase inhibitory activity, the results suggested that PGME possesses a significant inhibitory effect.Conclusion: The result obtained in the present study focuses on the anti-diabetic effect of PGME by studying cellular level glucose uptake in L6 myotubes and aldose reductase inhibitory activity.

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Shilianhua extract inhibits GSK-3β and promotes glucose metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00092.2009 ◽

2009 ◽

Vol 296 (6) ◽

pp. E1275-E1280 ◽

Cited By ~ 11

Author(s):

Jun Yin ◽

Aamir Zuberi ◽

Zhanguo Gao ◽

Dong Liu ◽

Zhijun Liu ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Metabolism ◽

Glucose Uptake ◽

Glucose Consumption ◽

Strong Activity ◽

Glucose Transporter 1 ◽

L6 Cells ◽

L6 Myotubes ◽

Gsk 3Β

The extract of plant Shilianhua (SLH; Sinocrassula indica Berge) is a component in a commercial product for control of blood glucose. However, it remains to be investigated whether the SLH extract enhances insulin sensitivity in a model of type 2 diabetes. To address this question, the SLH crude extract was fractionated into four parts on the basis of polarity, and bioactivities of each part were tested in cells. One of the fractions, F100, exhibited a strong activity in the stimulation of glucose consumption in vitro. Glucose consumption was induced significantly by F100 in 3T3-L1 adipocytes, L6 myotubes, and H4IIE hepatocytes in the absence of insulin. F100 also increased insulin-stimulated glucose consumption in L6 myotubes and H4IIE hepatocytes. It increased insulin-independent glucose uptake in 3T3-L1 adipocytes and insulin-dependent glucose uptake in L6 cells. The glucose transporter-1 (GLUT1) protein was induced in 3T3-L1 cells, and the GLUT4 protein was induced in L6 cells by F100. Mechanism study indicated that F100 induced GSK-3β phosphorylation, which was comparable with that induced by insulin. Additionally, the transcriptional activity of NF-κB was inhibited by F100. In RAW 264.7 macrophages, mRNA expression of NF-κB target genes (TNFα and MCP-1) was suppressed by F100. In KK.Cg-Ay/+ mice, F100 decreased fasting insulin and blood glucose and improved insulin tolerance significantly. We conclude that the F100 may be a bioactive component in the SLH plant. It promotes glucose metabolism in vitro and in vivo. Inhibition of GSK-3β and NF-κB may be the potential mechanism.

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