Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-d-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway

Li, Yunsheng; Kim, Jae‐Kyung; Li, Jing; Liu, Fang; Liu, Xueqing; Himmeldirk, Klaus; Ren, Yulin; Wagner, Thomas E.; Chen, Xiaozhuo

doi:10.1016/j.bbrc.2005.08.103

Cited by 100 publications

(102 citation statements)

References 38 publications

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“…05 versus insulin control, Fig. 5), as previously reported (Li et al 2005). Increased glucose uptake induced by Rb 1 was inhibited by both wortmannin and LY294004 (P!0 .…”

Section: Ginsenoside Rb 1 Activates Irs-1 Pi3k and Akt In Adipocytessupporting

confidence: 85%

Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

Shang

Yang²,

Zhou³

et al. 2008

Journal of Endocrinology

103

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A series of clinical trials and animal experiments have demonstrated that ginseng and its major active constituent, ginsenosides, possess glucose-lowering action. In our previous study, ginsenoside Rb 1 has been shown to regulate peroxisome proliferator-activated receptor g activity to facilitate adipogenesis of 3T3-L1 cells. However, the effect of Rb 1 on glucose transport in insulin-sensitive cells and its molecular mechanism need further elucidation. In this study, Rb 1 significantly stimulated basal and insulin-mediated glucose uptake in a time-and dose-dependent manner in 3T3-L1 adipocytes and C2C12 myotubes; the maximal effect was achieved at a concentration of 1 mM and a time of 3 h. In adipocytes, Rb 1 promoted GLUT1 and GLUT4 translocations to the cell surface, which was examined by analyzing their distribution in subcellular membrane fractions, and enhanced translocation of GLUT4 was confirmed using the transfection of GLUT4-green fluorescence protein in Chinese Hamster Ovary cells. Meanwhile, Rb 1 increased the phosphorylation of insulin receptor substrate-1 and protein kinase B (PKB), and stimulated phosphatidylinositol 3-kinase (PI3K) activity in the absence of the activation of the insulin receptor. Rb 1 -induced glucose uptake as well as GLUT1 and GLUT4 translocations was inhibited by the PI3K inhibitor. These results suggest that ginsenoside Rb 1 stimulates glucose transport in insulin-sensitive cells by promoting translocations of GLUT1 and GLUT4 by partially activating the insulin signaling pathway. These findings are useful in understanding the hypoglycemic and anti-diabetic properties of ginseng and ginsenosides.

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“…05 versus insulin control, Fig. 5), as previously reported (Li et al 2005). Increased glucose uptake induced by Rb 1 was inhibited by both wortmannin and LY294004 (P!0 .…”

Section: Ginsenoside Rb 1 Activates Irs-1 Pi3k and Akt In Adipocytessupporting

confidence: 85%

Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

Shang

Yang²,

Zhou³

et al. 2008

Journal of Endocrinology

103

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“…We previously showed that the human dietary compound a-PGG mimics insulin action by binding and activating the insulin receptor (IR), resulting in glucose uptake in target cells (26). We recently reported that a-PGG inhibits cancer cells through IR-mediated apoptosis in human colon cancer RKO cells (27).…”

Section: Resultsmentioning

confidence: 99%

A Small-Molecule Inhibitor of Glucose Transporter 1 Downregulates Glycolysis, Induces Cell-Cycle Arrest, and Inhibits Cancer Cell Growth In Vitro and In Vivo

Liu

Cao

Zhang

et al. 2012

Molecular Cancer Therapeutics

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467

389

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The functional and therapeutic importance of the Warburg effect is increasingly recognized, and glycolysis has become a target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation-like mechanism. We hypothesized that the compounds target Glut1 and are efficacious in vivo as anticancer agents. Here, we report that a novel representative compound WZB117 not only inhibited cell growth in cancer cell lines but also inhibited cancer growth in a nude mouse model. Daily intraperitoneal injection of WZB117 at 10 mg/kg resulted in a more than 70% reduction in the size of human lung cancer of A549 cell origin. Mechanism studies showed that WZB117 inhibited glucose transport in human red blood cells (RBC), which express Glut1 as their sole glucose transporter. Cancer cell treatment with WZB117 led to decreases in levels of Glut1 protein, intracellular ATP, and glycolytic enzymes. All these changes were followed by increase in ATPsensing enzyme AMP-activated protein kinase (AMPK) and declines in cyclin E2 as well as phosphorylated retinoblastoma, resulting in cell-cycle arrest, senescence, and necrosis. Addition of extracellular ATP rescued compound-treated cancer cells, suggesting that the reduction of intracellular ATP plays an important role in the anticancer mechanism of the molecule. Senescence induction and the essential role of ATP were reported for the first time in Glut1 inhibitor-treated cancer cells. Thus, WZB117 is a prototype for further development of anticancer therapeutics targeting Glut1-mediated glucose transport and glucose metabolism.

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“…In addition to inducing p53 expression and inhibiting STAT3 in prostate cancer cells, PGG suppresses the growth of prostate xenograft tumor in a nude mouse model (18). Meanwhile, PGG resembles insulin in that it activates insulin receptor to stimulate glucose transport in adipocytes and functions as an effective antidiabetic drug (21,30). This compound is also a vasorelaxant that dilates vascular smooth muscle and suppresses NO/ cGMP signaling (19).…”

mentioning

confidence: 99%

Inhibitory Effects of 1,2,3,4,6-Penta- O -Galloyl-β- d -Glucopyranose on Biofilm Formation by Staphylococcus aureus

Lin

Chang

Hua

et al. 2011

Antimicrob Agents Chemother

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1,2,3,4,6-Penta-O-galloyl-␤-D-glucopyranose (PGG)is an active ingredient in plants that are commonly used in Chinese medicine to treat inflammation. We demonstrate here that PGG, at 6.25 M, does not inhibit the growth of Staphylococcus aureus, and yet it prevents biofilm formation on polystyrene and polycarbonate surfaces. At the same concentration, PGG is not toxic to human epithelial and fibroblast cells. PGG has an IB 50 value, i.e., the PGG concentration that inhibits 50% biofilm formation, of 3.6 M. The value is substantially lower than that of N-acetylcysteine, iodoacetamide, and N-phenyl maleimide, which are known to inhibit biofilm formation by S. aureus. Biochemical and scanning electron microscopy results also reveal that PGG inhibits initial attachment of the bacteria to solid surface and the synthesis of polysaccharide intercellular adhesin, explaining how PGG inhibits biofilm formation. The results of this study demonstrate that coating PGG on polystyrene and silicon rubber surfaces with polyaniline prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation by S. aureus.

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Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-d-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway

Cited by 100 publications

References 38 publications

Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

A Small-Molecule Inhibitor of Glucose Transporter 1 Downregulates Glycolysis, Induces Cell-Cycle Arrest, and Inhibits Cancer Cell Growth In Vitro and In Vivo

Inhibitory Effects of 1,2,3,4,6-Penta- O -Galloyl-β- d -Glucopyranose on Biofilm Formation by Staphylococcus aureus

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