The Experts below are selected from a list of 61242 Experts worldwide ranked by ideXlab platform
Gerard Karsenty - One of the best experts on this subject based on the ideXlab platform.
-
Insulin Signaling in osteoblasts integrates bone remodeling and energy metabolism
2010Co-Authors: Mathieu Ferron, Jianwen Wei, Tatsuya Yoshizawa, Andrea Del Fattore, Ronald A Depinho, Anna Teti, Patricia Ducy, Gerard KarsentyAbstract:The broad expression of the Insulin receptor suggests that the spectrum of Insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that Insulin Signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function Insulin Signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing Insulin Signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, Insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.
-
Insulin Signaling in osteoblasts integrates bone remodeling and energy metabolism
2010Co-Authors: Mathieu Ferron, Tatsuya Yoshizawa, Ronald A Depinho, Anna Teti, Patricia Ducy, Andrea Del Fattore, Gerard KarsentyAbstract:SUMMARY The broad expression of the Insulin receptor suggests that the spectrum of Insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that Insulin Signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function Insulin Signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing Insulin Signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feedforward loop, Insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose
Mathieu Ferron - One of the best experts on this subject based on the ideXlab platform.
-
Insulin Signaling in osteoblasts integrates bone remodeling and energy metabolism
2010Co-Authors: Mathieu Ferron, Jianwen Wei, Tatsuya Yoshizawa, Andrea Del Fattore, Ronald A Depinho, Anna Teti, Patricia Ducy, Gerard KarsentyAbstract:The broad expression of the Insulin receptor suggests that the spectrum of Insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that Insulin Signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function Insulin Signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing Insulin Signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, Insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.
-
Insulin Signaling in osteoblasts integrates bone remodeling and energy metabolism
2010Co-Authors: Mathieu Ferron, Tatsuya Yoshizawa, Ronald A Depinho, Anna Teti, Patricia Ducy, Andrea Del Fattore, Gerard KarsentyAbstract:SUMMARY The broad expression of the Insulin receptor suggests that the spectrum of Insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that Insulin Signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function Insulin Signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing Insulin Signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feedforward loop, Insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose
Xing Li Wang - One of the best experts on this subject based on the ideXlab platform.
-
free fatty acids inhibit Insulin Signaling stimulated endothelial nitric oxide synthase activation through upregulating pten or inhibiting akt kinase
2006Co-Authors: Xing Li Wang, Lin Zhang, Keith A Youker, Mingxiang Zhang, Jian Wang, Scott A Lemaire, Joseph S Coselli, Ying H ShenAbstract:In metabolic syndrome, a systemic deregulation of the Insulin pathway leads to a combined deregulation of Insulin-regulated metabolism and cardiovascular functions. Free fatty acids (FFAs), which are increased in metabolic syndrome, inhibit Insulin Signaling and induce metabolic Insulin resistance. This study was designed to examine FFAs’ effects on vascular Insulin Signaling and endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells. We showed that FFAs inhibited Insulin Signaling and eNOS activation through different mechanisms. While linoleic acid inhibited Akt-mediated eNOS phosphorylation, palmitic acid appeared to affect the upstream Signaling. Upregulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity and transcription by palmitic acid mediated the inhibitory effects on Insulin Signaling. We further found that activated stress Signaling p38, but not Jun NH2-terminal kinase, was involved in PTEN upregulation. The p38 target transcriptional factor activating transcription factor (ATF)-2 bound to the PTEN promoter, which was increased by palmitic acid treatment. In summary, both palmitic acid and linoleic acid exert inhibitory effect on Insulin Signaling and eNOS activation in endothelial cells. Palmitic acid inhibits Insulin Signaling by promoting PTEN activity and its transcription through p38 and its downstream transcription factor ATF-2. Our findings suggest that FFA-mediated inhibition of vascular Insulin Signaling and eNOS activation may contribute to cardiovascular diseases in metabolic syndrome.
-
up regulation of pten phosphatase and tensin homolog deleted on chromosome ten mediates p38 mapk stress signal induced inhibition of Insulin Signaling a cross talk between stress Signaling and Insulin Signaling in resistin treated human endothelial cells
2006Co-Authors: Ying H Shen, Lin Zhang, Jian Wang, Scott A Lemaire, Joseph S Coselli, Xinwen Wang, Xing Li WangAbstract:Abstract The key feature of metabolic syndrome, a cluster of metabolic and cardiovascular disorders, is systemic Insulin resistance, which is associated with dysregulated endothelial nitric-oxide synthase (eNOS). Stress Signaling induced by inflammation can inhibit Insulin Signaling. However, molecular mechanisms for the cross-talk between stress Signaling and Insulin resistance are only partially understood. Resistin, an adipokine/cytokine, is involved in inflammatory processes that could lead to Insulin resistance status and vascular diseases. In the current study, we observed that resistin inhibited Insulin Signaling and eNOS activation in endothelial cells. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression by resistin may mediate the inhibitory effects. Activated stress Signaling p38 MAPK, but not JNK, is involved in PTEN up-regulation. We further found that p38 target transcriptional factor activating transcription factor-2 (ATF-2) bound to ATF sites in the PTEN promoter. The phosphorylation/activation of ATF-2 and its binding to PTEN promoter were increased by resistin treatment. In summary, up-regulation of PTEN is involved in the inhibitory effects of resistin on Insulin Signaling and eNOS activation in endothelial cells. Resistin induces PTEN expression by activating stress Signaling p38 pathway, which may activate target transcription factor ATF-2, which in turn induces PTEN expression. Our findings suggest that resistin-mediated inhibition of Insulin Signaling and eNOS activation may contribute to cardiovascular diseases.
Sheldon E Litwin - One of the best experts on this subject based on the ideXlab platform.
-
Insulin Signaling coordinately regulates cardiac size metabolism and contractile protein isoform expression
2002Co-Authors: Darrell D Belke, Sandrine Betuing, Martin J Tuttle, Christophe Graveleau, Martin E Young, Mark Pham, Dongfang Zhang, Robert C Cooksey, Donald A Mcclain, Sheldon E LitwinAbstract:To investigate the role of Insulin Signaling on postnatal cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective Insulin receptor knockout (CIRKO) using cre/loxP recombination. Hearts of CIRKO mice were reduced in size by 20‐30% due to reduced cardiomyocyte size and had persistent expression of the fetal β-myosin heavy chain isoform. In CIRKO hearts, glucose transporter 1 (GLUT1) expression was reduced by about 50%, but there was a twofold increase in GLUT4 expression as well as increased rates of cardiac glucose uptake in vivo and increased glycolysis in isolated working hearts. Fatty acid oxidation rates were diminished as a result of reduced expression of enzymes that catalyze mitochondrial β-oxidation. Although basal rates of glucose oxidation were reduced, Insulin unexpectedly stimulated glucose oxidation and glycogenolysis in CIRKO hearts. Cardiac performance in vivo and in isolated hearts was mildly impaired. Thus, Insulin Signaling plays an important developmental role in regulating postnatal cardiac size, myosin isoform expression, and the switching of cardiac substrate utilization from glucose to fatty acids. Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating Insulin receptors in other cell types within the heart.
-
Insulin Signaling coordinately regulates cardiac size metabolism and contractile protein isoform expression
2002Co-Authors: Darrell D Belke, Sandrine Betuing, Martin J Tuttle, Christophe Graveleau, Martin E Young, Mark Pham, Dongfang Zhang, Robert C Cooksey, Donald A Mcclain, Sheldon E LitwinAbstract:To investigate the role of Insulin Signaling on postnatal cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective Insulin receptor knockout (CIRKO) using cre/loxP recombination. Hearts of CIRKO mice were reduced in size by 20-30% due to reduced cardiomyocyte size and had persistent expression of the fetal beta-myosin heavy chain isoform. In CIRKO hearts, glucose transporter 1 (GLUT1) expression was reduced by about 50%, but there was a twofold increase in GLUT4 expression as well as increased rates of cardiac glucose uptake in vivo and increased glycolysis in isolated working hearts. Fatty acid oxidation rates were diminished as a result of reduced expression of enzymes that catalyze mitochondrial beta-oxidation. Although basal rates of glucose oxidation were reduced, Insulin unexpectedly stimulated glucose oxidation and glycogenolysis in CIRKO hearts. Cardiac performance in vivo and in isolated hearts was mildly impaired. Thus, Insulin Signaling plays an important developmental role in regulating postnatal cardiac size, myosin isoform expression, and the switching of cardiac substrate utilization from glucose to fatty acids. Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating Insulin receptors in other cell types within the heart.
Ying H Shen - One of the best experts on this subject based on the ideXlab platform.
-
free fatty acids inhibit Insulin Signaling stimulated endothelial nitric oxide synthase activation through upregulating pten or inhibiting akt kinase
2006Co-Authors: Xing Li Wang, Lin Zhang, Keith A Youker, Mingxiang Zhang, Jian Wang, Scott A Lemaire, Joseph S Coselli, Ying H ShenAbstract:In metabolic syndrome, a systemic deregulation of the Insulin pathway leads to a combined deregulation of Insulin-regulated metabolism and cardiovascular functions. Free fatty acids (FFAs), which are increased in metabolic syndrome, inhibit Insulin Signaling and induce metabolic Insulin resistance. This study was designed to examine FFAs’ effects on vascular Insulin Signaling and endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells. We showed that FFAs inhibited Insulin Signaling and eNOS activation through different mechanisms. While linoleic acid inhibited Akt-mediated eNOS phosphorylation, palmitic acid appeared to affect the upstream Signaling. Upregulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity and transcription by palmitic acid mediated the inhibitory effects on Insulin Signaling. We further found that activated stress Signaling p38, but not Jun NH2-terminal kinase, was involved in PTEN upregulation. The p38 target transcriptional factor activating transcription factor (ATF)-2 bound to the PTEN promoter, which was increased by palmitic acid treatment. In summary, both palmitic acid and linoleic acid exert inhibitory effect on Insulin Signaling and eNOS activation in endothelial cells. Palmitic acid inhibits Insulin Signaling by promoting PTEN activity and its transcription through p38 and its downstream transcription factor ATF-2. Our findings suggest that FFA-mediated inhibition of vascular Insulin Signaling and eNOS activation may contribute to cardiovascular diseases in metabolic syndrome.
-
up regulation of pten phosphatase and tensin homolog deleted on chromosome ten mediates p38 mapk stress signal induced inhibition of Insulin Signaling a cross talk between stress Signaling and Insulin Signaling in resistin treated human endothelial cells
2006Co-Authors: Ying H Shen, Lin Zhang, Jian Wang, Scott A Lemaire, Joseph S Coselli, Xinwen Wang, Xing Li WangAbstract:Abstract The key feature of metabolic syndrome, a cluster of metabolic and cardiovascular disorders, is systemic Insulin resistance, which is associated with dysregulated endothelial nitric-oxide synthase (eNOS). Stress Signaling induced by inflammation can inhibit Insulin Signaling. However, molecular mechanisms for the cross-talk between stress Signaling and Insulin resistance are only partially understood. Resistin, an adipokine/cytokine, is involved in inflammatory processes that could lead to Insulin resistance status and vascular diseases. In the current study, we observed that resistin inhibited Insulin Signaling and eNOS activation in endothelial cells. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression by resistin may mediate the inhibitory effects. Activated stress Signaling p38 MAPK, but not JNK, is involved in PTEN up-regulation. We further found that p38 target transcriptional factor activating transcription factor-2 (ATF-2) bound to ATF sites in the PTEN promoter. The phosphorylation/activation of ATF-2 and its binding to PTEN promoter were increased by resistin treatment. In summary, up-regulation of PTEN is involved in the inhibitory effects of resistin on Insulin Signaling and eNOS activation in endothelial cells. Resistin induces PTEN expression by activating stress Signaling p38 pathway, which may activate target transcription factor ATF-2, which in turn induces PTEN expression. Our findings suggest that resistin-mediated inhibition of Insulin Signaling and eNOS activation may contribute to cardiovascular diseases.