Ginsenoside Rg1 Promotes Glucose Uptake Through Activated AMPK Pathway in Insulin‐resistant Muscle Cells

Lee, Hyemin; Lee, Ok‐Hwan; Kim, Kui-Jin; Lee, Boo-Yong

doi:10.1002/ptr.3686

Cited by 62 publications

(43 citation statements)

References 22 publications

(22 reference statements)

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“…At these concentrations, the offtarget effects are minimal compared with most other studies using ginsenosides or triterpenoids (Zhang et al, 2008;Lee et al, 2012a;Gao et al, 2013;Liu et al, 2013). Previously, it has been known that Rg1 enhances glucose uptake in 3T3-L1 adipocytes and insulin-resistant muscle cells (Huang et al, 2010b;Lee et al, 2012a). Since the intestine is the site where most nutrients are absorbed, it is interesting to understand the Rg1 Reduces SGLT1 Gene Expression via CREB Deactivation Fig.…”

Section: Discussionmentioning

confidence: 99%

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression

Wang

Huang

et al. 2015

Mol Pharmacol

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The Na 1 /glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is significantly increased in diabetic individuals and positively correlated with the pathogenesis of diabetes. The development of targeted therapeutics that can reduce the intestinal SGLT1 expression level is, therefore, important. In this study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose uptake through inhibition of SGLT1 gene expression in vivo and in vitro. Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP response element (CRE) that confers the Rg1-mediated inhibition of SGLT1 gene expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein (CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and CREB binding protein associated with an inactivated chromatin status. In addition, further studies showed that the epidermal growth factor receptor (EGFR) signaling pathway also plays an essential role in the inhibitory effect of Rg1; taken together, our study demonstrates the involvement of the EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of antihyperglycemic and antidiabetic treatments.

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Section: Discussionmentioning

confidence: 99%

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression

Wang

Huang

et al. 2015

Mol Pharmacol

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“…Recently, it was shown that ginsenoside Rg1 also promotes glucose uptake in insulinresistant C2C12 cells (39), suggesting that remaining ginsenosides could be active on insulin-resistant cells. However, the effect of these compounds on human cells, sensitive or resistant to insulin, is yet unknown.…”

Section: Discussionmentioning

confidence: 99%

Isoorientin Reverts TNF-α-Induced Insulin Resistance in Adipocytes Activating the Insulin Signaling Pathway

et al. 2012

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Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-D-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-␣, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulinresistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-␣ by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins. (Endocrinology 153: 5222-5230, 2012)

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“…That may be associated with the properties of aronia and ginseng to suppress body fat synthesis and to increase skeletal muscle mass [37][38][39]. Furthermore, Px rats had lower BMD in the lumbar spine and femur and lower LBM in the hip and leg in comparison to the normal-control.…”

Section: Discussionmentioning

confidence: 99%

Combination of Aronia, Red Ginseng and Shiitake Mushroom Potentiated Insulin Secretion and Reduced Insulin Resistance with Improving Gut Microbiome Dysbiosis in Insulin Deficient Type 2 Diabetic Rats

Yang¹,

Kim²,

Kwon³

et al. 2018

Preprint

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The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group.Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normalcontrol group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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Ginsenoside Rg1 Promotes Glucose Uptake Through Activated AMPK Pathway in Insulin‐resistant Muscle Cells

Cited by 62 publications

References 22 publications

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression

Isoorientin Reverts TNF-α-Induced Insulin Resistance in Adipocytes Activating the Insulin Signaling Pathway

Combination of Aronia, Red Ginseng and Shiitake Mushroom Potentiated Insulin Secretion and Reduced Insulin Resistance with Improving Gut Microbiome Dysbiosis in Insulin Deficient Type 2 Diabetic Rats

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Ginsenoside Rg1 Promotes Glucose Uptake Through Activated AMPK Pathway in Insulin‐resistant Muscle Cells

Cited by 62 publications

References 22 publications

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

Isoorientin Reverts TNF-α-Induced Insulin Resistance in Adipocytes Activating the Insulin Signaling Pathway

Combination of Aronia, Red Ginseng and Shiitake Mushroom Potentiated Insulin Secretion and Reduced Insulin Resistance with Improving Gut Microbiome Dysbiosis in Insulin Deficient Type 2 Diabetic Rats

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An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na⁺/Glucose Cotransporter 1 Gene Expression