Search

Your search keyword '"Dominique Bécard"' showing total 5 results
Start Over Author "Dominique Bécard"
5 results on '"Dominique Bécard"'

1. Sterol-regulatory-element-binding protein I c mediates insulin action on hepatic gene expression

Author

Fabienne Foufelle, Pascal Ferré, Dominique Bécard, Marc Foretz, Dalila Azzout-Marniche, FORETZ, Marc, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
medicine.medical_treatment, MESH: Insulin, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biochemistry, MESH: Mammals, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, 0302 clinical medicine, Mediator, Gene expression, medicine, MESH: Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Transcription factor, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, biology, Glucokinase, MESH: Glucagon, GRB10, Insulin, MESH: Energy Metabolism, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Gene Expression Regulation, IRS2, MESH: Glucose, Insulin receptor, MESH: Homeostasis, 030220 oncology & carcinogenesis, MESH: Glycolysis, biology.protein, MESH: DNA-Binding Proteins, MESH: Liver
Abstract

Effects of insulin on the expression of liver-specific genes are part of the adaptive mechanisms aimed at maintaining energy homeostasis in mammals. When the diet is rich in carbohydrates, secreted insulin stimulates the expression of genes for enzymes involved in glucose utilization (glucokinase, L-type pyruvate kinase and lipogenic enzymes) and inhibits genes for enzymes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes have been poorly understood. Recently, the transcription factor sterol-regulatory-element-binding protein 1c has been proposed as a key mediator of insulin transcriptional effects. Here we review the evidence that has led to this proposal and the consequences for our understanding of insulin effects in physiological or pathological conditions.

Published
2001
Full Text
View/download PDF

2. Long chain fatty acyl-CoA synthetase 5 expression is induced by insulin and glucose: involvement of sterol regulatory element-binding protein-1c

Author

Isabelle Hainault, Pascal Ferré, Dominique Bécard, D Allanic, Fabienne Foufelle, Younes Achouri, and Bronwyn D. Hegarty

Subjects
medicine.medical_specialty, Anabolism, medicine.medical_treatment, Biochemistry, Polymerase Chain Reaction, Diabetes Mellitus, Experimental, Mitochondrial Proteins, Eating, Internal medicine, Diabetes mellitus, Coenzyme A Ligases, medicine, Animals, Insulin, RNA, Messenger, Rats, Wistar, biology, Fatty Acids, General Medicine, Fasting, Carbohydrate, medicine.disease, Sterol regulatory element-binding protein, Rats, Insulin receptor, Endocrinology, medicine.anatomical_structure, Glucose, Liver, Hepatocyte, Enzyme Induction, Lipogenesis, Models, Animal, biology.protein, lipids (amino acids, peptides, and proteins), Female, Sterol Regulatory Element Binding Protein 1
Abstract

In a screen for sterol regulatory element-binding protein (SREBP)-1c target genes in the liver, we identified long chain fatty acyl-CoA synthetase 5 (ACS-5). Hepatic ACS-5 mRNA is poorly expressed during fasting and diabetes and strongly induced by carbohydrate refeeding and insulin treatment. In cultured hepatocytes, insulin and a high glucose concentration induce ACS-5 mRNA. Adenoviral overexpression of a nuclear form of SREBP-1c in liver of diabetic mice or in cultured hepatocytes mimics the effect of insulin to induce ACS-5. By contrast, a dominant negative form of SREBP-1c abolishes the effect of insulin on ACS-5 expression. The dietary and SREBP-1c-mediated insulin regulation of ACS-5 expression indicate that ACS-5 is involved in the anabolic fate of fatty acids.

Published
2005

3. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice

Author

Isabelle Hainault, Dalila Azzout-Marniche, Pascal Ferré, Lydia Bertry-Coussot, Dominique Bécard, Fabienne Foufelle, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Azzout-Marniche, Dalila, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)

Subjects
Male, MESH : RNA, Messenger, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: CCAAT-Enhancer-Binding Proteins, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, Homeostasis, Insulin, Glucose homeostasis, MESH: Animals, 0303 health sciences, MESH: Mice, Inbred CBA, Glycogen, Gene Transfer Techniques, MESH: Adenoviridae, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Genetic Vectors, 3. Good health, MESH : DNA-Binding Proteins, MESH : Diabetes Mellitus, Experimental, Sterol Regulatory Element Binding Protein 1, medicine.medical_specialty, MESH: Gene Expression, MESH: Gene Transfer Techniques, MESH: Insulin, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Adenoviridae, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 1, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], RNA, Messenger, MESH : Gene Transfer Techniques, MESH : Injections, Intraperitoneal, MESH : Glucose, Glucokinase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH : Gene Expression, Glucose, Endocrinology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], chemistry, CCAAT-Enhancer-Binding Proteins, Mice, Inbred CBA, MESH: Liver, Transcription Factors, MESH : Transcription Factors, MESH : Insulin, MESH : Mice, Inbred CBA, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, chemistry.chemical_compound, MESH: Genetic Vectors, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Diabetes Mellitus, Experimental, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Recombinant Proteins, MESH: Glucose, DNA-Binding Proteins, Liver, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Homeostasis, MESH : Homeostasis, Phosphoenolpyruvate carboxykinase, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, MESH : Recombinant Proteins, MESH : Male, Genetic Vectors, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Diabetes mellitus, Internal medicine, MESH : Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Internal Medicine, medicine, Animals, MESH : Adenoviridae, MESH: Mice, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Liver, Metabolism, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins
Abstract

International audience; In vitro, the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) mimics the positive effects of insulin on hepatic genes involved in glucose utilization, such as glucokinase (GK) and enzymes of the lipogenic pathway, suggesting that it is a key factor in the control of hepatic glucose metabolism. Decreased glucose utilization and increased glucose production by the liver play an important role in the development of the hyperglycemia in diabetic states. We thus reasoned that if SREBP-1c is indeed a mediator of hepatic insulin action, a hepatic targeted overexpression of SREBP-1c should greatly improve glucose homeostasis in diabetic mice. This was achieved by injecting streptozotocin-induced diabetic mice with a recombinant adenovirus containing the cDNA of the mature, transcriptionally active form of SREBP-1c. We show here that overexpressing SREBP-1c specifically in the liver of diabetic mice induces GK and lipogenic enzyme gene expression and represses the expression of phosphoenolpyruvate carboxykinase, a key enzyme of the gluconeogenic pathway. This in turn increases glycogen and triglyceride hepatic content and leads to a marked decrease in hyperglycemia in diabetic mice. We conclude that SREBP-1c has a major role in vivo in the long-term control of glucose homeostasis by insulin.

Published
2001

4. Sterol Regulatory Element-binding Protein-1c Mimics the Negative Effect of Insulin on Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription

Author

Dominique Bécard, Fabienne Foufelle, Patrick Leahy, Pascal Ferré, Richard W. Hanson, Marc Foretz, Kaushik Chakravarty, Parvin Hakimi, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies nutritionnelles et métaboliques : obésité et diabète, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cyclic AMP Receptor Protein, Transcription, Genetic, RNA polymerase II, Biochemistry, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Hepatocytes, E2F1, Insulin, MESH: Animals, 0303 health sciences, biology, MESH: Phosphoenolpyruvate Carboxykinase (GTP), 030302 biochemistry & molecular biology, MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Activating transcription factor 2, DNA-Binding Proteins, TAF2, Female, Phosphoenolpyruvate Carboxykinase (GTP), lipids (amino acids, peptides, and proteins), Sterol Regulatory Element Binding Protein 1, endocrine system, MESH: Rats, E-box, MESH: Carrier Proteins, MESH: Cyclic AMP-Dependent Protein Kinases, MESH: Insulin, digestive system, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, Sp3 transcription factor, Animals, RNA, Messenger, Rats, Wistar, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, 030304 developmental biology, MESH: RNA, Messenger, ATF3, MESH: Transcription, Genetic, Promoter, MESH: Cyclic AMP Receptor Protein, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, MESH: Rats, Wistar, Molecular biology, Cyclic AMP-Dependent Protein Kinases, Rats, biology.protein, CCAAT-Enhancer-Binding Proteins, Hepatocytes, Carrier Proteins, MESH: Female, MESH: DNA-Binding Proteins, Transcription Factors
Abstract

International audience; We have assessed the potential role of sterol regulatory element-binding protein-1c (SREBP-1c) on the transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC ) (PEPCK-C). SREBP-1c introduced into primary hepatocytes with an adenovirus vector caused a total loss of PEPCK-C mRNA and a marked induction of fatty acid synthase mRNA that directly coincided with the appearance of SREBP-1c in the hepatocytes. It also blocked the induction of PEPCK-C mRNA by cAMP and dexamethasone in these cells. In contrast, a dominant negative form of SREBP-1c (dnSREBP-1c) stimulated the accumulation of PEPCK-C mRNA in these cells. SREBP-1c completely blocked the induction of PEPCK-C gene transcription by the catalytic subunit of protein kinase A (PKA), and increasing concentrations of dnSREBP-1c reversed the negative effect of insulin on transcription from the PEPCK-C gene promoter in WT-IR cells. The more than 10-fold induction of PKA-stimulated PEPCK-C gene transcription caused by the co-activator CBP, was also blocked by SREBP-1c. In addition, dnSREBP-1c reversed the strong negative effect of E1A and NF1 on PKA-stimulated transcription from the PEPCK-C gene promoter. An analysis of the possible site of action of SREBP-1c using stepwise truncations of the PEPCK-C gene promoter indicated that the negative effect of SREBP-1c on transcription is exerted at a site between -355 and -277. We conclude that SREBP-1c is an intermediate in the action of insulin on PEPCK-C gene transcription in the liver and acts by blocking the stimulatory effect cAMP that is mediated via an interaction with cAMP-binding protein.

Published
2001
Full Text
View/download PDF

5. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes

Author

Dalila Azzout-Marniche, Marc Foretz, Fabienne Foufelle, Pascal Ferré, Colette Guichard, Dominique Bécard, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
MESH: Protein Precursors, Transcription, Genetic, medicine.medical_treatment, MESH : Hepatocytes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Hepatocytes, 0302 clinical medicine, Insulin receptor substrate, Insulin, MESH: Animals, Enzyme Inhibitors, MESH : Immunoblotting, Cells, Cultured, Protein Synthesis Inhibitors, 0303 health sciences, MESH : Cell Nucleus, MESH : Glucokinase, MESH: Immunoblotting, food and beverages, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Glucokinase, MESH: Transcription Factors, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, MESH : DNA-Binding Proteins, Sterol Regulatory Element Binding Protein 1, MESH: Cells, Cultured, MESH: Cell Nucleus, MESH: Enzyme Activation, MESH : Cell Membrane, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Insulin, digestive system, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, MESH : Sterol Regulatory Element Binding Protein 1, MESH: Blotting, Northern, Protein Precursors, Molecular Biology, Dose-Response Relationship, Drug, Glucokinase, Endoplasmic reticulum, Cell Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sterol regulatory element-binding protein, Enzyme Activation, MESH: Phosphatidylinositol 3-Kinases, CCAAT-Enhancer-Binding Proteins, MESH: Female, Transcription Factors, MESH: Signal Transduction, Time Factors, MESH : Transcription Factors, MESH : Insulin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Dose-Response Relationship, Drug, Endoplasmic Reticulum, MESH: Dose-Response Relationship, Drug, Phosphatidylinositol 3-Kinases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], polycyclic compounds, MESH : Female, Cycloheximide, MESH: Cycloheximide, MESH : Protein Precursors, MESH : Endoplasmic Reticulum, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Blotting, Northern, DNA-Binding Proteins, Fatty acid synthase, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Enzyme Inhibitors, Female, lipids (amino acids, peptides, and proteins), MESH : Time Factors, Research Article, Signal Transduction, MESH: Rats, Immunoblotting, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Endoplasmic Reticulum, MESH : Cycloheximide, MESH : Cells, Cultured, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH : Protein Synthesis Inhibitors, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Protein Synthesis Inhibitors, MESH: Transcription, Genetic, MESH: Time Factors, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Phosphatidylinositol 3-Kinases, Cell Biology, Blotting, Northern, Rats, biology.protein, Hepatocytes, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, MESH: Cell Membrane
Abstract

International audience; The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of insulin on the transcription of genes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.

Published
2000

Catalog

Books, media, physical & digital resources
See catalog results