Limonoids isolated from fruits of Swietenia macrophylla king enhance glucose consumption in insulin‐resistant HepG2 cells via activating PPARγ

We analyzed the effects of a traditional Chinese medicine, Qizhi Jiangtang Jiaonang (QJJ), on insulin resistance (IR) in vitro. After an in vitro model of IR was established by treating human liver cancer cells (HepG2 cells) with palmitic acid, the cells were then treated with various concentrations of QJJ. Treatment with 400 µM palmitic acid for 24 h induced IR in HepG2 cells. The survival rate for HepG2 cells in the IR group was significantly lower than that of the untreated control group (P< 0.001); however, QJJ restored HepG2 cell survival (P< 0.001). As compared with HepG2 cells in the IR group, QJJ at all doses analyzed significantly increased glucose consumption (allP< 0.05). Moreover, treatment with all the QJJ doses significantly reduced the mean intracellular reactive oxygen species levels as compared with the IR group (allP< 0.05). Furthermore, high-dose QJJ reduced both TNF-αand IL-6 levels as compared to the IR group (allP< 0.05). QJJ ameliorated the altered PI3K, GLUT4, and RAGE expression observed with IR. In conclusion, QJJ can improve IR in HepG2 cells, which may be mediated through the IRS-1/PI3K/GLUT4 signaling pathway as well as regulation of NF-κB-mediated inflammation and oxidative stress.

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Cajanonic acid A regulates the ratio of Th17/Treg via inhibition of expression of IL-6 and TGF-β in insulin-resistant HepG2 cells

Bioscience Reports ◽

10.1042/bsr20181716 ◽

2019 ◽

Vol 39 (12) ◽

Author(s):

Yanfeng Gong ◽

Huanbing Liu ◽

Liming Tao

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Hepg2 Cells ◽

Neutralizing Antibody ◽

Glucose Consumption ◽

Transduction Pathway ◽

Flow Cytometry Assay ◽

Insulin Resistant ◽

Cellular Apoptosis ◽

Reduce Insulin Resistance

Abstract Background: The objectives of the present study are to investigate whether cajanonic acid A (CAA) can reduce insulin resistance (IR) in HepG2 cells and to gain a preliminary understanding of the mechanisms underlying this effect. Methods: Following induction of IR in HepG2 cells, we tested the regulatory effect of CAA on glucose consumption and evaluated hepatocyte production of IL-6, TGF-β, and key molecules in the insulin transduction pathway. A transwell co-culturing system was used to assess the effect of CAA on IR in HepG2 cells during the differentiation of CD4+ T cells by calculating the ratio of (Th17)/regulatory T cell (Treg). We evaluated the effect of CAA on the expression of IL-17RC cells and HepG2 cell apoptosis by immunofluorescence and flow cytometry assay. Results: CAA improved dexamethasone-induced reduction in glucose consumption in HepG2 cells, inhibited hepatocyte production of IL-6 and TGF-β, increased the expression of IL-17RC cell, and increased cellular apoptosis in insulin-resistant HepG2 cells. When co-cultured with CD4+ T cells, insulin-resistant HepG2 cells induced a decrease in the ratio of Th17/Treg, but CAA dampened the effect. Application of IL-6 and TGF-β, together with CAA, reversed the effect of CAA on insulin-resistant HepG2 cells. Overexpression of IL17R, however, counteracted the effect of IL-6 neutralizing antibody within the culture system. Conclusion: CAA can regulate the ratio of Th17/Treg by mediating the expression of IL-6 and TGF-β in insulin-resistant HepG2 cells.

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Chemical Characterization and Hypoglycaemic Activities In Vitro of Two Polysaccharides from Inonotus obliquus by Submerged Culture

Molecules ◽

10.3390/molecules23123261 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3261 ◽

Cited By ~ 5

Author(s):

Jiao Xue ◽

Shisheng Tong ◽

Zhaorun Wang ◽

Ping Liu

Keyword(s):

Molecular Weight ◽

Hepg2 Cells ◽

Chemical Characterization ◽

Glucose Consumption ◽

Biologically Active ◽

Infrared Analysis ◽

Inonotus Obliquus ◽

Insulin Resistant ◽

Natural Drugs

Polysaccharides from the fungus Inonotus obliquus have been found to be biologically active. In this study, we carried out a preliminary characterisation and assessment of the hypoglycaemic activities of the polysaccharides (IOEP) from Inonotus obliquus obtained by liquid fermentation. Two polysaccharides, IOEP1 and IOEP2, were isolated from IOEP. IOEP1, with a molecular weight of 20 KDa, was mainly composed of galatose and mannose, while IOEP2, with a molecular weight of 200 KDa, was mainly composed of arabinose. Fourier-transform infrared analysis showed that both IOEP1 and IOEP2 were pyran-type polysaccharides. 1H-NMR spectra showed that the glycosidic bonds of IOEP1 and IOEP2 were both α-type and β-type. In addition, IOEP1 and IOEP2 strongly increased the glucose consumption of HepG2 cells and insulin-resistant HepG2 cells in vitro. These findings provide a theoretical basis that IOEP1 and IOEP2 might be suitable as anti-diabetes agents in functional foods and natural drugs.

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Microwave-assisted synthesis of chitosan biguanidine hydrochloride and its regulation on InsR and GLUT2 in insulin resistant HepG2 cells

RSC Advances ◽

10.1039/c6ra25998g ◽

2017 ◽

Vol 7 (17) ◽

pp. 10108-10117 ◽

Cited By ~ 3

Author(s):

Shengsheng Zhang ◽

Hai Zhang ◽

Li Wang ◽

Xiaofei Liu ◽

Yuntang Wu

Keyword(s):

Hepg2 Cells ◽

Glucose Consumption ◽

Microwave Assisted Synthesis ◽

Over Expression ◽

Insulin Resistant ◽

Microwave Assisted ◽

High Insulin

CSGH increased glucose consumption of HepG2 cells by accelerating the expression of InsR and inhibiting the high-insulin-induced over-expression of GLUT2.

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Putative identification of components in Zengye Decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells

Journal of Chromatography B ◽

10.1016/j.jchromb.2017.12.019 ◽

2018 ◽

Vol 1073 ◽

pp. 145-153 ◽

Cited By ~ 6

Author(s):

Zhenzhen Liu ◽

Wenhua Kuang ◽

Xi Xu ◽

Dandan Li ◽

Wufu Zhu ◽

...

Keyword(s):

Hepg2 Cells ◽

Glucose Consumption ◽

Insulin Resistant

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Online Measurement of Glucose Consumption from HepG2 Cells Using an Integrated Bioreactor and Enzymatic Assay

10.26434/chemrxiv.7469726.v1 ◽

2018 ◽

Author(s):

Anna Adams ◽

Radha Krishna Murthy Bulusu ◽

Nikita Mukhitov ◽

Jose Mendoza-Cortes ◽

Michael Roper

Keyword(s):

Real Time ◽

Glucose Concentration ◽

Hepg2 Cells ◽

Glucose Consumption ◽

Microfluidic System ◽

Structure And Function ◽

Online Measurement ◽

Fluorescent Assay ◽

And Function ◽

Integrated Bioreactor

In this work, we developed a microfluidic bioreactor for optimizing growth and maintaining structure and function of HepG2, and when desired, the device could be removed and the extracellular output from the bioreactor combined with enzymatic glucose reagents into a droplet-based microfluidic system. The intensity of the resulting fluorescent assay product in the droplets was measured, and was directly correlated to glucose concentration, allowing the effect of insulin on glucose consumption in the HepG2 cells to be observed and quantified online and in near real-time.

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Online Measurement of Glucose Consumption from HepG2 Cells Using an Integrated Bioreactor and Enzymatic Assay

10.26434/chemrxiv.7469726 ◽

2018 ◽

Author(s):

Anna Adams ◽

Radha Krishna Murthy Bulusu ◽

Nikita Mukhitov ◽

Jose Mendoza-Cortes ◽

Michael Roper

Keyword(s):

Real Time ◽

Glucose Concentration ◽

Hepg2 Cells ◽

Glucose Consumption ◽

Microfluidic System ◽

Structure And Function ◽

Online Measurement ◽

Fluorescent Assay ◽

And Function ◽

Integrated Bioreactor

In this work, we developed a microfluidic bioreactor for optimizing growth and maintaining structure and function of HepG2, and when desired, the device could be removed and the extracellular output from the bioreactor combined with enzymatic glucose reagents into a droplet-based microfluidic system. The intensity of the resulting fluorescent assay product in the droplets was measured, and was directly correlated to glucose concentration, allowing the effect of insulin on glucose consumption in the HepG2 cells to be observed and quantified online and in near real-time.

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The Mechanism of Jian-Gan-Xiao-Zhi Decoction in Insulin Resistant Adipocytes and Its Component Analysis

Natural Product Communications ◽

10.1177/1934578x21997678 ◽

2021 ◽

Vol 16 (3) ◽

pp. 1934578X2199767

Author(s):

Fang Fang ◽

Wei-Bo Wen ◽

Xue-Hua Xie ◽

Ling Yang ◽

Xu Zhang ◽

...

Keyword(s):

Lipid Synthesis ◽

Glucose Consumption ◽

Astragaloside Iv ◽

Serum Samples ◽

Rat Serum ◽

Jnk Pathway ◽

Alcoholic Fatty Liver ◽

Insulin Resistant ◽

Glucose Levels ◽

Main Components

Background: Jian-Gan-Xiao-Zhi decoction (JGXZ) is a traditional Chinese medicine formula to treat patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to analyze the mechanism of JGXZ in adipocytes and detect the main components of the drug in rat serum. Methods: 3T3-L1 preadipocytes were used to establish an insulin resistant (IR) adipocyte model. Lipid accumulation in adipocytes was detected by oil red O staining. After JGXZ treatment, glucose consumption, total cholesterol (TC), and triglyceride (TG) were analyzed using the corresponding kits. ROS levels were measured by flow cytometry. In addition, Western blot was used to assess LKB1/AMPK and JNK/IRS/PI3k/AKT expressions. The main components of JGXZ in rat serum samples were detected by LC-MS/MS using a Phenomenex Luna C18 column, a mobile phase of methanol and 0.1% formic acid solution, and ESI detection. Results: JGXZ significantly decreased glucose levels and adipogenesis, accompanied by decreased IR ( P < 0.01). Besides, JGXZ markedly affected ROS, LKB1/AMPK, and JNK/IRS/PI3k/AKT levels ( P < 0.01). R1, Rg1, paeoniflorin, Rb1, astragaloside IV, and tanshinone could be significantly quantified. Conclusions: JGXZ decreased glucose and lipid synthesis, possibly via the ROS/AMPK/JNK pathway. R1, Rg1, paeoniflorin, Rb1, astragaloside IV, and tanshinone in JGXZ could play major roles in treating NAFLD, which could assist in the study of the mechanism of JGXZ in treating NAFLD.

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