The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform

Yong Man - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA 152 regulates hepatic Glycogenesis by targeting PTEN
    The FEBS journal, 2016
    Co-Authors: Shuyue Wang, Lin Dou, Xiangyu Meng, Tao Shen, Jun Guo, Weiwei Fang, Yong Man, Lilin Wang, Xiuqing Huang
    Abstract:

    Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic Glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired Glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired Glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic Glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated Glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.

  • MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression
    Journal of cellular and molecular medicine, 2016
    Co-Authors: Weiwei Fang, Lin Dou, Shuyue Wang, Xiuqing Huang, Jun Guo, Yong Man, Yuan Cao, Cheng Pang, Tao Shen
    Abstract:

    Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and Glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated Glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired Glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced Glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated Glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in Glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

  • mir 19a regulates pten expression to mediate glycogen synthesis in hepatocytes
    Scientific Reports, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    MiR-19a, a member of mir-17-92 microRNA clusters, has been demonstrated to promote cell proliferation and angiogenesis via regulating the PI3K/AKT pathway, the major insulin signaling pathway. However, whether miR-19a plays an important role in glycogen synthesis in hepatocytes remains unknown. Here, we define the impact of miR-19a on glycogen synthesis and IL-6-induced reduced Glycogenesis in hepatocytes and its underlying mechanisms. Our studies indicate that miR-19a was down-regulated in the livers of db/db mice and mice injected with IL-6, as well as mouse NCTC 1469 hepatocytes and HEP 1–6 hepatocytes treated by IL-6. We found that over-expression of miR-19a in NCTC 1469 cells and HEP 1–6 cells led to increased activation of the AKT/GSK pathway and synthesis of glycogen, whereas down-regulation of miR-19a impaired AKT/GSK phosphorylation and Glycogenesis. Over-expression of miR-19a ameliorated IL-6-induced reduced glycogen synthesis in hepatocytes. Moreover, we identified PTEN as the target of miR-19a by a luciferase assay. Down-regulation of PTEN rescued the effects of miR-19a suppression on the activation of the AKT/GSK pathway and improved Glycogenesis in NTC 1469 cells. These findings show for the first time that miR-19a might activate the AKT/GSK pathway and Glycogenesis via down-regulation of PTEN expression.

  • MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis by regulating PTEN expression.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression. © 2015 S. Karger AG, Basel.

  • mir 301a mediates the effect of il 6 on the akt gsk pathway and hepatic Glycogenesis by regulating pten expression
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    Background/Aims: IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. Methods: The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. Results: In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. Conclusion: We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.

Tao Shen - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA 152 regulates hepatic Glycogenesis by targeting PTEN
    The FEBS journal, 2016
    Co-Authors: Shuyue Wang, Lin Dou, Xiangyu Meng, Tao Shen, Jun Guo, Weiwei Fang, Yong Man, Lilin Wang, Xiuqing Huang
    Abstract:

    Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic Glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired Glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired Glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic Glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated Glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.

  • MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression
    Journal of cellular and molecular medicine, 2016
    Co-Authors: Weiwei Fang, Lin Dou, Shuyue Wang, Xiuqing Huang, Jun Guo, Yong Man, Yuan Cao, Cheng Pang, Tao Shen
    Abstract:

    Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and Glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated Glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired Glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced Glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated Glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in Glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

  • mir 19a regulates pten expression to mediate glycogen synthesis in hepatocytes
    Scientific Reports, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    MiR-19a, a member of mir-17-92 microRNA clusters, has been demonstrated to promote cell proliferation and angiogenesis via regulating the PI3K/AKT pathway, the major insulin signaling pathway. However, whether miR-19a plays an important role in glycogen synthesis in hepatocytes remains unknown. Here, we define the impact of miR-19a on glycogen synthesis and IL-6-induced reduced Glycogenesis in hepatocytes and its underlying mechanisms. Our studies indicate that miR-19a was down-regulated in the livers of db/db mice and mice injected with IL-6, as well as mouse NCTC 1469 hepatocytes and HEP 1–6 hepatocytes treated by IL-6. We found that over-expression of miR-19a in NCTC 1469 cells and HEP 1–6 cells led to increased activation of the AKT/GSK pathway and synthesis of glycogen, whereas down-regulation of miR-19a impaired AKT/GSK phosphorylation and Glycogenesis. Over-expression of miR-19a ameliorated IL-6-induced reduced glycogen synthesis in hepatocytes. Moreover, we identified PTEN as the target of miR-19a by a luciferase assay. Down-regulation of PTEN rescued the effects of miR-19a suppression on the activation of the AKT/GSK pathway and improved Glycogenesis in NTC 1469 cells. These findings show for the first time that miR-19a might activate the AKT/GSK pathway and Glycogenesis via down-regulation of PTEN expression.

  • MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis by regulating PTEN expression.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression. © 2015 S. Karger AG, Basel.

  • mir 301a mediates the effect of il 6 on the akt gsk pathway and hepatic Glycogenesis by regulating pten expression
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    Background/Aims: IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. Methods: The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. Results: In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. Conclusion: We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.

Xiuqing Huang - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA 152 regulates hepatic Glycogenesis by targeting PTEN
    The FEBS journal, 2016
    Co-Authors: Shuyue Wang, Lin Dou, Xiangyu Meng, Tao Shen, Jun Guo, Weiwei Fang, Yong Man, Lilin Wang, Xiuqing Huang
    Abstract:

    Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic Glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired Glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired Glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic Glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated Glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.

  • MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression
    Journal of cellular and molecular medicine, 2016
    Co-Authors: Weiwei Fang, Lin Dou, Shuyue Wang, Xiuqing Huang, Jun Guo, Yong Man, Yuan Cao, Cheng Pang, Tao Shen
    Abstract:

    Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and Glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated Glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired Glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced Glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated Glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in Glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

  • mir 19a regulates pten expression to mediate glycogen synthesis in hepatocytes
    Scientific Reports, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    MiR-19a, a member of mir-17-92 microRNA clusters, has been demonstrated to promote cell proliferation and angiogenesis via regulating the PI3K/AKT pathway, the major insulin signaling pathway. However, whether miR-19a plays an important role in glycogen synthesis in hepatocytes remains unknown. Here, we define the impact of miR-19a on glycogen synthesis and IL-6-induced reduced Glycogenesis in hepatocytes and its underlying mechanisms. Our studies indicate that miR-19a was down-regulated in the livers of db/db mice and mice injected with IL-6, as well as mouse NCTC 1469 hepatocytes and HEP 1–6 hepatocytes treated by IL-6. We found that over-expression of miR-19a in NCTC 1469 cells and HEP 1–6 cells led to increased activation of the AKT/GSK pathway and synthesis of glycogen, whereas down-regulation of miR-19a impaired AKT/GSK phosphorylation and Glycogenesis. Over-expression of miR-19a ameliorated IL-6-induced reduced glycogen synthesis in hepatocytes. Moreover, we identified PTEN as the target of miR-19a by a luciferase assay. Down-regulation of PTEN rescued the effects of miR-19a suppression on the activation of the AKT/GSK pathway and improved Glycogenesis in NTC 1469 cells. These findings show for the first time that miR-19a might activate the AKT/GSK pathway and Glycogenesis via down-regulation of PTEN expression.

  • MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis by regulating PTEN expression.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression. © 2015 S. Karger AG, Basel.

  • mir 301a mediates the effect of il 6 on the akt gsk pathway and hepatic Glycogenesis by regulating pten expression
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    Background/Aims: IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. Methods: The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. Results: In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. Conclusion: We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.

Lin Dou - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA 152 regulates hepatic Glycogenesis by targeting PTEN
    The FEBS journal, 2016
    Co-Authors: Shuyue Wang, Lin Dou, Xiangyu Meng, Tao Shen, Jun Guo, Weiwei Fang, Yong Man, Lilin Wang, Xiuqing Huang
    Abstract:

    Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic Glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired Glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired Glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic Glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated Glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.

  • MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression
    Journal of cellular and molecular medicine, 2016
    Co-Authors: Weiwei Fang, Lin Dou, Shuyue Wang, Xiuqing Huang, Jun Guo, Yong Man, Yuan Cao, Cheng Pang, Tao Shen
    Abstract:

    Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and Glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated Glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired Glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced Glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated Glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in Glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

  • mir 19a regulates pten expression to mediate glycogen synthesis in hepatocytes
    Scientific Reports, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    MiR-19a, a member of mir-17-92 microRNA clusters, has been demonstrated to promote cell proliferation and angiogenesis via regulating the PI3K/AKT pathway, the major insulin signaling pathway. However, whether miR-19a plays an important role in glycogen synthesis in hepatocytes remains unknown. Here, we define the impact of miR-19a on glycogen synthesis and IL-6-induced reduced Glycogenesis in hepatocytes and its underlying mechanisms. Our studies indicate that miR-19a was down-regulated in the livers of db/db mice and mice injected with IL-6, as well as mouse NCTC 1469 hepatocytes and HEP 1–6 hepatocytes treated by IL-6. We found that over-expression of miR-19a in NCTC 1469 cells and HEP 1–6 cells led to increased activation of the AKT/GSK pathway and synthesis of glycogen, whereas down-regulation of miR-19a impaired AKT/GSK phosphorylation and Glycogenesis. Over-expression of miR-19a ameliorated IL-6-induced reduced glycogen synthesis in hepatocytes. Moreover, we identified PTEN as the target of miR-19a by a luciferase assay. Down-regulation of PTEN rescued the effects of miR-19a suppression on the activation of the AKT/GSK pathway and improved Glycogenesis in NTC 1469 cells. These findings show for the first time that miR-19a might activate the AKT/GSK pathway and Glycogenesis via down-regulation of PTEN expression.

  • MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis by regulating PTEN expression.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression. © 2015 S. Karger AG, Basel.

  • mir 301a mediates the effect of il 6 on the akt gsk pathway and hepatic Glycogenesis by regulating pten expression
    Cellular Physiology and Biochemistry, 2015
    Co-Authors: Lin Dou, Xiangyu Meng, Xiaofang Sui, Shuyue Wang, Tao Shen, Xiuqing Huang, Jun Guo, Weiwei Fang, Yong Man
    Abstract:

    Background/Aims: IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. Methods: The activation of AKT/GSK pathway and the level of Glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. Results: In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and Glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic Glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced Glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic Glycogenesis. Conclusion: We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.

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  • independent signal transduction pathways for vanadate and for insulin in the activation of glycogen synthase and Glycogenesis in rat adipocytes
    Endocrinology, 1999
    Co-Authors: Natesampillai Sekar, Dov Gefel, Yoram Shechter
    Abstract:

    The activating effect of vanadate on Glycogenesis and on glycogen synthase (uridine diphosphate-glucose-glycogen glucosyl transferase) activity was studied in rat adipocytes and compared with that of insulin. Using several approaches and specific blockers, we found that vanadate and insulin resemble each other, in the activation of glycogen synthase, in several aspects: both require nonarrested protein phosphatase 1 activity; they are equally suppressed by conditions that elevate cAMP-levels; and both depend on the activation of phosphatidylinositol-3 kinase. The basic differences between them are as follows: 1) vanadate promotes Glycogenesis through the activation of a cytosolic protein tyrosine kinase, in an insulin-receptor-independent manner; 2) vanadate elevates glucose-6-phosphate (G-6-P) to a higher level than insulin; 3) vanadate-activated Glycogenesis is accompanied by an increase in the cellular content of immunoreactive glycogen synthase, an effect less noticeable with insulin; 4) adipose gluco...

  • INDEPENDENT SIGNAL-TRANSDUCTION PATHWAYS FOR VANADATE AND FOR INSULIN IN THE ACTIVATION OF GLYCOGEN SYNTHASE AND Glycogenesis IN RAT ADIPOCYTES
    Endocrinology, 1999
    Co-Authors: Natesampillai Sekar, Dov Gefel, Yoram Shechter
    Abstract:

    The activating effect of vanadate on Glycogenesis and on glycogen synthase (uridine diphosphate-glucose-glycogen glucosyl transferase) activity was studied in rat adipocytes and compared with that of insulin. Using several approaches and specific blockers, we found that vanadate and insulin resemble each other, in the activation of glycogen synthase, in several aspects: both require nonarrested protein phosphatase 1 activity; they are equally suppressed by conditions that elevate cAMP-levels; and both depend on the activation of phosphatidylinositol-3 kinase. The basic differences between them are as follows: 1) vanadate promotes Glycogenesis through the activation of a cytosolic protein tyrosine kinase, in an insulin-receptor-independent manner; 2) vanadate elevates glucose-6-phosphate (G-6-P) to a higher level than insulin; 3) vanadate-activated Glycogenesis is accompanied by an increase in the cellular content of immunoreactive glycogen synthase, an effect less noticeable with insulin; 4) adipose glucose-6-phosphatase is inhibited by vanadate (dose for 50% inhibition, IC50 = 7 +/- 0.7 microM) but not by insulin. We have concluded that insulin and vanadate activate Glycogenesis through a phosphatidylinositol-3 kinase and dephosphorylation-dependent mechanism. Vanadate, however, uses a receptor-independent pathway and is superior to insulin in elevating the level of G-6-P, a key metabolite for activating glycogen synthase. This is attributed to the combined effect of vanadate in enhancing glucose entry and in inhibiting dephosphorylation of endogenously formed G-6-P. The latter effect is not exerted by insulin.