The Experts below are selected from a list of 46734 Experts worldwide ranked by ideXlab platform
Esther B Baart - One of the best experts on this subject based on the ideXlab platform.
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obestatin induction of early response gene expression in gastrointestinal and adipose tissues and the mediatory role of g protein coupled receptor gpr39
Molecular Endocrinology, 2008Co-Authors: Cynthia Klein, Luc Ver Donck, Ananya De, Esther B Baart, Kristof Van Kolen, Holger JahrAbstract:Obestatin was identified as a brain/gut peptide Hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a Metabolic Hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues.
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obestatin induction of early response gene expression in gastrointestinal and adipose tissues and the mediatory role of g protein coupled receptor gpr39
Molecular Endocrinology, 2008Co-Authors: Jian Zhang, Cynthia Klein, Luc Ver Donck, Ananya De, Esther B Baart, Kristof Van Kolen, Holger Jahr, Jing LiAbstract:Obestatin was identified as a brain/gut peptide Hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a Metabolic Hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues.
Holger Jahr - One of the best experts on this subject based on the ideXlab platform.
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obestatin induction of early response gene expression in gastrointestinal and adipose tissues and the mediatory role of g protein coupled receptor gpr39
Molecular Endocrinology, 2008Co-Authors: Cynthia Klein, Luc Ver Donck, Ananya De, Esther B Baart, Kristof Van Kolen, Holger JahrAbstract:Obestatin was identified as a brain/gut peptide Hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a Metabolic Hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues.
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obestatin induction of early response gene expression in gastrointestinal and adipose tissues and the mediatory role of g protein coupled receptor gpr39
Molecular Endocrinology, 2008Co-Authors: Jian Zhang, Cynthia Klein, Luc Ver Donck, Ananya De, Esther B Baart, Kristof Van Kolen, Holger Jahr, Jing LiAbstract:Obestatin was identified as a brain/gut peptide Hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a Metabolic Hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues.
Jung Hwa Hong - One of the best experts on this subject based on the ideXlab platform.
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the autophagy protein becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding
Cell Reports, 2021Co-Authors: Kenta Kuramoto, Yoonjin Kim, Jung Hwa HongAbstract:Autophagy dysregulation is implicated in Metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a Metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived Metabolic Hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue.
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the autophagy protein becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding
Social Science Research Network, 2020Co-Authors: Kenta Kuramoto, Yoonjin Kim, Jung Hwa HongAbstract:Beclin 1/Becn1 is an essential protein in autophagy, a stress-induced lysosomal degradation pathway. Autophagy dysregulation is implicated in the pathogenesis of Metabolic diseases such as type 2 diabetes. However, the mechanism of the autophagy machinery in Metabolic regulation is poorly understood. In this study, we discovered a Metabolically important secretory function of Becn1 in adipose tissue, which is distinct from its role in degradation. In response to high-fat diet challenge, autophagy-hyperactive Becn1F121A mice, caused by a constitutively active Becn1F121A mutation, show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell autonomous mechanism. We further identified that the circulating factor that activates AMPK systemically in Becn1F121A mice is adiponectin, a Metabolic Hormone secreted from adipocytes. The Becn1-facilitated adiponectin secretion is regulated by upstream autophagy modulators, and is mediated by binding of the coiled-coil domain of Becn1 with subunits of the exocyst complex. In addition, adipose tissue-specific Becn1F121A expression is sufficient to activate liver AMPK and improve systemic insulin sensitivity by increasing adiponectin secretion. Altogether, we demonstrated that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through interacting with the exocyst in adipose tissue. Our study highlights a novel non-cell autonomous, non-degradative, mechanism by which the autophagy machinery regulates metabolism.
Juan J Diez - One of the best experts on this subject based on the ideXlab platform.
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biological role clinical significance and therapeutic possibilities of the recently discovered Metabolic Hormone fibroblastic growth factor 21
European Journal of Endocrinology, 2012Co-Authors: Pedro Iglesias, Rafael Selgas, Sara Romero, Juan J DiezAbstract:Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant Metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in Metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive Metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the Metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified Hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.
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mechanisms in endocrinology biological role clinical significance and therapeutic possibilities of the recently discovered Metabolic Hormone fibroblastic growth factor 21
European Journal of Endocrinology, 2012Co-Authors: Pedro Iglesias, Rafael Selgas, Sara Romero, Juan J DiezAbstract:: Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant Metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in Metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive Metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the Metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified Hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.
Kenta Kuramoto - One of the best experts on this subject based on the ideXlab platform.
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the autophagy protein becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding
Cell Reports, 2021Co-Authors: Kenta Kuramoto, Yoonjin Kim, Jung Hwa HongAbstract:Autophagy dysregulation is implicated in Metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a Metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived Metabolic Hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue.
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the autophagy protein becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding
Social Science Research Network, 2020Co-Authors: Kenta Kuramoto, Yoonjin Kim, Jung Hwa HongAbstract:Beclin 1/Becn1 is an essential protein in autophagy, a stress-induced lysosomal degradation pathway. Autophagy dysregulation is implicated in the pathogenesis of Metabolic diseases such as type 2 diabetes. However, the mechanism of the autophagy machinery in Metabolic regulation is poorly understood. In this study, we discovered a Metabolically important secretory function of Becn1 in adipose tissue, which is distinct from its role in degradation. In response to high-fat diet challenge, autophagy-hyperactive Becn1F121A mice, caused by a constitutively active Becn1F121A mutation, show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell autonomous mechanism. We further identified that the circulating factor that activates AMPK systemically in Becn1F121A mice is adiponectin, a Metabolic Hormone secreted from adipocytes. The Becn1-facilitated adiponectin secretion is regulated by upstream autophagy modulators, and is mediated by binding of the coiled-coil domain of Becn1 with subunits of the exocyst complex. In addition, adipose tissue-specific Becn1F121A expression is sufficient to activate liver AMPK and improve systemic insulin sensitivity by increasing adiponectin secretion. Altogether, we demonstrated that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through interacting with the exocyst in adipose tissue. Our study highlights a novel non-cell autonomous, non-degradative, mechanism by which the autophagy machinery regulates metabolism.