Bombyxin II Regulates Glucose Absorption and Glycogen Synthesis through the PI3K Signaling Pathway in HepG2 Cells

Bombyxin, as an insulin-like insect hormone, was discovered in the silkmoth Bombyx mori. It can regulate the metabolism of trehalose and glycogen in Bombyx mori, but whether it has glucose absorption and glycogen synthesis effect on mammalian cells was not clear. BombyxinII (BbxII) and mutant BbxII (mBbxII) genes were cloned into pcDNA3.1(+) vector, respectively; then, gene vectors were transfected into 293FT cells using Lipofectamine 2000. Levels of mRNA and protein expression of BbxII and mBbxII were detected by PCR and Western blot in 293FT cells, respectively. Glucose consumption and glycogenesis were determined by glucose oxidase-peroxidase (GOD-POD) and periodic acid-Schiff (PAS) staining in HepG2 cells; the PI3K signaling pathway was inhibited with wortmannin S1952 in HepG2 cells. Result showed that BbxII and mBbxII genes were being successfully expressed in 293FT cells, respectively. The expression protein of BbxII gene is 10kd pre-bombyxinII, and yet, the expression protein of mBbxII gene is 4kd mature bombyxinII. Only the 4kd bombyxinII showed increased glucose uptake and glycogenesis in HepG2 cells, and the ability of increasing glucose uptake was equal to the human insulin (10 nM). PI3K-wortmannin S1952 inhibitor can decrease the glycogen synthesis induced by bombyxin II protein in HepG2 cells. In conclusion, mature bombyxin II may adjust glucose absorption and glycogen synthesis in HepG2 cells through the PI3K signaling pathway.

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Exposure to Perfluoro-Octanoic Acid Associated With Upstream Uncoupling of the Insulin Signaling in Human Hepatocyte Cell Line

Frontiers in Endocrinology ◽

10.3389/fendo.2021.632927 ◽

2021 ◽

Vol 12 ◽

Author(s):

Luca De Toni ◽

Andrea Di Nisio ◽

Maria Santa Rocca ◽

Diego Guidolin ◽

Alice Della Marina ◽

...

Keyword(s):

Glucose Uptake ◽

Hepg2 Cells ◽

Octanoic Acid ◽

Periodic Acid ◽

Glycogen Synthesis ◽

Human Hepatocyte ◽

Pathogenic Mechanism ◽

Low Grade ◽

Glut 4 ◽

Long Term Treatment

Perfluoro–alkyl substances (PFAS) are chemical pollutants with prevalent stability and environmental persistence. Exposure to PFAS, particularly perfluoro-octanoic acid (PFOA), has been associated with increased diabetes-related cardiovascular mortality in subjects residing areas of high environmental contamination, however the exact pathogenic mechanism remains elusive. Here we used HepG2 cells, an in vitro model of human hepatocyte, to investigate the possible role of PFOA exposure in the alteration of hepatic glucose metabolism. HepG2 cells were exposed for 24 hours to PFOA at increasing concentration from 0 to 1000 ng/mL and then stimulated with 100 nm Insulin (Ins). The consequent effect on glycogen synthesis, glucose uptake and Glut-4 glucose transporter translocation was then evaluated by, respectively, Periodic Acid Schiff (PAS) staining, 2-deoxyglucose (2-DG) uptake assay and immunofluorescence. Exposure to PFOA was associated with reduced glycogen synthesis and glucose uptake, at concentration equal or greater than, respectively, 0,1 ng/mL and 10 ng/mL, with parallel impaired membrane translocation of Glut-4 upon Ins stimulation. Western blot analysis showed early uncoupling of Insulin Receptor (InsR) activation from the downstream Akt and GSK3 phosphorylation. Computational docking analysis disclosed the possible stabilizing effect of PFOA on the complex between InsR and GM3 ganglioside, previously shown to be associated with the low grade chronic inflammation-related insulin resistance. Consistently, long term treatment with glucosyl-ceramide synthase inhibitor PDMP was able to largely restore glycogen synthesis, glucose uptake and Glut-4 translocation upon Ins stimulation in HepG2 exposed to PFOA. Our data support a novel pathogenic mechanism linking exposure to PFOA to derangement of hepatocyte cell metabolism.

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Ursolic Acid Increases Glucose Uptake through the PI3K Signaling Pathway in Adipocytes

PLoS ONE ◽

10.1371/journal.pone.0110711 ◽

2014 ◽

Vol 9 (10) ◽

pp. e110711 ◽

Cited By ~ 15

Author(s):

Yonghan He ◽

Wen Li ◽

Ying Li ◽

Shuocheng Zhang ◽

Yanwen Wang ◽

...

Keyword(s):

Glucose Uptake ◽

Signaling Pathway ◽

Ursolic Acid ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

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Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

Molecules ◽

10.3390/molecules25184254 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4254 ◽

Cited By ~ 1

Author(s):

Gloria C. Bonel-Pérez ◽

Amalia Pérez-Jiménez ◽

Isabel Gris-Cárdenas ◽

Alberto M. Parra-Pérez ◽

José Antonio Lupiáñez ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

New Drugs ◽

Pi3k Signaling ◽

Apoptotic Protein ◽

Apoptotic Effect ◽

Anticancer Mechanism ◽

Pi3k Signaling Pathway ◽

Cell Arrest ◽

New Treatments

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea L. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in the HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Our results show that uvaol has a clear and selective anticancer activity in HepG2 cells supported by a significant anti-migratory capacity and a significant increase in the expression of HSP-60. Furthermore, the administration of this triterpene induces cell arrest in the G0/G1 phase, as well as an increase in the rate of cell apoptosis. These results are supported by a decrease in the expression of the anti-apoptotic protein Bcl2, an increase in the expression of the pro-apoptotic protein Bax, together with a down-regulation of the AKT/PI3K signaling pathway. A reduction in reactive oxygen species (ROS) levels in HepG2 cells was also observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

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PI3K signaling Pathway gene expression analysis in cumulus cells by Real-Time PCR

10.26226/morressier.573c1511d462b80296c982f0 ◽

2016 ◽

Author(s):

Paolo Giovanni Artini

Keyword(s):

Gene Expression ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Gene Expression Analysis ◽

Cumulus Cells ◽

Pi3k Signaling ◽

Pathway Gene ◽

Pi3k Signaling Pathway ◽

Signaling Pathway Gene

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Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

Current Medicinal Chemistry ◽

10.2174/0929867324666170206142658 ◽

2017 ◽

Vol 24 (13) ◽

Cited By ~ 50

Author(s):

Safieh Ebrahimi ◽

Mina Hosseini ◽

Soodabeh Shahidsales ◽

Mina Maftouh ◽

Gordon A. Ferns ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Therapeutic Strategy ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

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BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells

Open Life Sciences ◽

10.1515/biol-2020-0054 ◽

2020 ◽

Vol 15 (1) ◽

pp. 501-510

Author(s):

Bin Ma ◽

Wenjia Guo ◽

Meihui Shan ◽

Nan Zhang ◽

Binlin Ma ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Nuclear Localization ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Pi3k Pathway ◽

Pi3k Signaling ◽

T47d Cells ◽

Pi3k Signaling Pathway ◽

Hormone Sensitive

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

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Design, synthesis and biological evaluation of novel 2,4-disubstituted quinazoline derivatives targeting H1975 cells via EGFR-PI3K signaling pathway

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2021.116265 ◽

2021 ◽

Vol 43 ◽

pp. 116265

Author(s):

Zhengjie Wang ◽

Limin Liu ◽

Honglin Dai ◽

Xiaojie Si ◽

Luye Zhang ◽

...

Keyword(s):

Signaling Pathway ◽

Biological Evaluation ◽

Pi3k Signaling ◽

Design Synthesis ◽

Pi3k Signaling Pathway ◽

Quinazoline Derivatives ◽

Synthesis And Biological Evaluation

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Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003295 ◽

2014 ◽

Vol 58 (8) ◽

pp. 833-837 ◽

Cited By ~ 2

Author(s):

Miriane de Oliveira ◽

Regiane Marques Castro Olimpio ◽

Maria Teresa De Sibio ◽

Fernanda Cristina Fontes Moretto ◽

Renata de Azevedo Mello Luvizotto ◽

...

Keyword(s):

Thyroid Hormone ◽

Mrna Expression ◽

Signaling Pathway ◽

Thyroid Hormone Receptor ◽

Pi3k Pathway ◽

Control Group ◽

Pi3k Signaling ◽

Pi3k Inhibitor Ly294002 ◽

Receptor Alpha ◽

Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

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