Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism.
Identifieur interne : 001D12 ( Main/Exploration ); précédent : 001D11; suivant : 001D13Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism.
Auteurs : Blake J. Cochran [Australie] ; Liming Hou [Australie] ; Anil Paul Chirackal Manavalan [Australie] ; Benjamin M. Moore [Australie] ; Fatiha Tabet [Australie] ; Afroza Sultana [Australie] ; Luisa Cuesta Torres [Australie] ; Shudi Tang [Australie] ; Sudichhya Shrestha [Australie] ; Praween Senanayake [Australie] ; Mili Patel [Australie] ; William J. Ryder [Australie] ; Andre Bongers [Australie] ; Marie Maraninchi [France] ; Valerie C. Wasinger [Australie] ; Marit Westerterp [États-Unis] ; Alan R. Tall [États-Unis] ; Philip J. Barter [Australie] ; Kerry-Anne Rye [Australie]Source :
- Diabetes [ 1939-327X ] ; 2016.
Descripteurs français
- KwdFr :
- Acide lactique (sang), Animaux, Cellules à insuline (métabolisme), Cholestérol (métabolisme), Fatty acid synthases, Glucose (métabolisme), Glycogène (métabolisme), Homéostasie (génétique), Homéostasie (physiologie), Imagerie par résonance magnétique, Insuline (métabolisme), Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP (déficit), Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP (métabolisme), Muscles squelettiques (métabolisme), Réaction de polymérisation en chaîne, Souris, Souris knockout, Spectrométrie de masse, Technique de Western, Tissu adipeux (métabolisme), Transporteur-1 à cassette liant l'ATP (déficit), Transporteur-1 à cassette liant l'ATP (métabolisme).
- MESH :
- déficit : Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP, Transporteur-1 à cassette liant l'ATP.
- génétique : Homéostasie.
- métabolisme : Cellules à insuline, Cholestérol, Glucose, Glycogène, Insuline, Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP, Muscles squelettiques, Tissu adipeux, Transporteur-1 à cassette liant l'ATP.
- physiologie : Homéostasie.
- sang : Acide lactique.
- Animaux, Fatty acid synthases, Imagerie par résonance magnétique, Réaction de polymérisation en chaîne, Souris, Souris knockout, Spectrométrie de masse, Technique de Western.
English descriptors
- KwdEn :
- ATP Binding Cassette Transporter 1 (deficiency), ATP Binding Cassette Transporter 1 (metabolism), ATP Binding Cassette Transporter, Sub-Family G, Member 1 (deficiency), ATP Binding Cassette Transporter, Sub-Family G, Member 1 (metabolism), Adipose Tissue (metabolism), Animals, Blotting, Western, Cholesterol (metabolism), Fatty Acid Synthases, Glucose (metabolism), Glycogen (metabolism), Homeostasis (genetics), Homeostasis (physiology), Insulin (metabolism), Insulin-Secreting Cells (metabolism), Lactic Acid (blood), Magnetic Resonance Imaging, Mass Spectrometry, Mice, Mice, Knockout, Muscle, Skeletal (metabolism), Polymerase Chain Reaction.
- MESH :
- chemical , blood : Lactic Acid.
- chemical , deficiency : ATP Binding Cassette Transporter 1, ATP Binding Cassette Transporter, Sub-Family G, Member 1.
- chemical , metabolism : ATP Binding Cassette Transporter 1, ATP Binding Cassette Transporter, Sub-Family G, Member 1, Cholesterol, Glucose, Glycogen, Insulin.
- genetics : Homeostasis.
- metabolism : Adipose Tissue, Insulin-Secreting Cells, Muscle, Skeletal.
- physiology : Homeostasis.
- Animals, Blotting, Western, Fatty Acid Synthases, Magnetic Resonance Imaging, Mass Spectrometry, Mice, Mice, Knockout, Polymerase Chain Reaction.
Abstract
Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes.
DOI: 10.2337/db16-0668
PubMed: 27702832
Affiliations:
- Australie, France, États-Unis
- Nouvelle-Galles du Sud, Provence-Alpes-Côte d'Azur, État de New York
- Marseille, Sydney
- Université d'Aix-Marseille
Links toward previous steps (curation, corpus...)
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- to stream Main, to step Curation: 001D12
Le document en format XML
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Wasinger</name><affiliation wicri:level="3"><nlm:affiliation>Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Westerterp, Marit" sort="Westerterp, Marit" uniqKey="Westerterp M" first="Marit" last="Westerterp">Marit Westerterp</name><affiliation wicri:level="2"><nlm:affiliation>Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Division of Molecular Medicine, Department of Medicine, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Tall, Alan R" sort="Tall, Alan R" uniqKey="Tall A" first="Alan R" last="Tall">Alan R. Tall</name><affiliation wicri:level="2"><nlm:affiliation>Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Division of Molecular Medicine, Department of Medicine, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Barter, Philip J" sort="Barter, Philip J" uniqKey="Barter P" first="Philip J" last="Barter">Philip J. Barter</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia k.rye@unsw.edu.au karye@ozemail.com.au.</nlm:affiliation><country wicri:rule="url">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27702832</idno><idno type="pmid">27702832</idno><idno type="doi">10.2337/db16-0668</idno><idno type="wicri:Area/PubMed/Corpus">001447</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001447</idno><idno type="wicri:Area/PubMed/Curation">001425</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001425</idno><idno type="wicri:Area/PubMed/Checkpoint">001425</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001425</idno><idno type="wicri:Area/Ncbi/Merge">003C56</idno><idno type="wicri:Area/Ncbi/Curation">003C56</idno><idno type="wicri:Area/Ncbi/Checkpoint">003C56</idno><idno type="wicri:Area/Main/Merge">001D09</idno><idno type="wicri:Area/Main/Curation">001D12</idno><idno type="wicri:Area/Main/Exploration">001D12</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism.</title><author><name sortKey="Cochran, Blake J" sort="Cochran, Blake J" uniqKey="Cochran B" first="Blake J" last="Cochran">Blake J. Cochran</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Hou, Liming" sort="Hou, Liming" uniqKey="Hou L" first="Liming" last="Hou">Liming Hou</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Manavalan, Anil Paul Chirackal" sort="Manavalan, Anil Paul Chirackal" uniqKey="Manavalan A" first="Anil Paul Chirackal" last="Manavalan">Anil Paul Chirackal Manavalan</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Moore, Benjamin M" sort="Moore, Benjamin M" uniqKey="Moore B" first="Benjamin M" last="Moore">Benjamin M. Moore</name><affiliation wicri:level="3"><nlm:affiliation>Division of Medicine, Royal Prince Alfred Hospital, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Division of Medicine, Royal Prince Alfred Hospital, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Tabet, Fatiha" sort="Tabet, Fatiha" uniqKey="Tabet F" first="Fatiha" last="Tabet">Fatiha Tabet</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Sultana, Afroza" sort="Sultana, Afroza" uniqKey="Sultana A" first="Afroza" last="Sultana">Afroza Sultana</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Cuesta Torres, Luisa" sort="Cuesta Torres, Luisa" uniqKey="Cuesta Torres L" first="Luisa" last="Cuesta Torres">Luisa Cuesta Torres</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Tang, Shudi" sort="Tang, Shudi" uniqKey="Tang S" first="Shudi" last="Tang">Shudi Tang</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Shrestha, Sudichhya" sort="Shrestha, Sudichhya" uniqKey="Shrestha S" first="Sudichhya" last="Shrestha">Sudichhya Shrestha</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Senanayake, Praween" sort="Senanayake, Praween" uniqKey="Senanayake P" first="Praween" last="Senanayake">Praween Senanayake</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Patel, Mili" sort="Patel, Mili" uniqKey="Patel M" first="Mili" last="Patel">Mili Patel</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Ryder, William J" sort="Ryder, William J" uniqKey="Ryder W" first="William J" last="Ryder">William J. Ryder</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Bongers, Andre" sort="Bongers, Andre" uniqKey="Bongers A" first="Andre" last="Bongers">Andre Bongers</name><affiliation wicri:level="3"><nlm:affiliation>Biological Resource Imaging Laboratory, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Biological Resource Imaging Laboratory, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Maraninchi, Marie" sort="Maraninchi, Marie" uniqKey="Maraninchi M" first="Marie" last="Maraninchi">Marie Maraninchi</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, UMR_S1062, UMR_A1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, UMR_S1062, UMR_A1260, Nutrition, Obésité et Risque Thrombotique, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Wasinger, Valerie C" sort="Wasinger, Valerie C" uniqKey="Wasinger V" first="Valerie C" last="Wasinger">Valerie C. Wasinger</name><affiliation wicri:level="3"><nlm:affiliation>Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Westerterp, Marit" sort="Westerterp, Marit" uniqKey="Westerterp M" first="Marit" last="Westerterp">Marit Westerterp</name><affiliation wicri:level="2"><nlm:affiliation>Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Division of Molecular Medicine, Department of Medicine, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Tall, Alan R" sort="Tall, Alan R" uniqKey="Tall A" first="Alan R" last="Tall">Alan R. Tall</name><affiliation wicri:level="2"><nlm:affiliation>Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Division of Molecular Medicine, Department of Medicine, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Barter, Philip J" sort="Barter, Philip J" uniqKey="Barter P" first="Philip J" last="Barter">Philip J. Barter</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, Australia k.rye@unsw.edu.au karye@ozemail.com.au.</nlm:affiliation><country wicri:rule="url">Australie</country><wicri:regionArea>Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author></analytic><series><title level="j">Diabetes</title><idno type="eISSN">1939-327X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ATP Binding Cassette Transporter 1 (deficiency)</term><term>ATP Binding Cassette Transporter 1 (metabolism)</term><term>ATP Binding Cassette Transporter, Sub-Family G, Member 1 (deficiency)</term><term>ATP Binding Cassette Transporter, Sub-Family G, Member 1 (metabolism)</term><term>Adipose Tissue (metabolism)</term><term>Animals</term><term>Blotting, Western</term><term>Cholesterol (metabolism)</term><term>Fatty Acid Synthases</term><term>Glucose (metabolism)</term><term>Glycogen (metabolism)</term><term>Homeostasis (genetics)</term><term>Homeostasis (physiology)</term><term>Insulin (metabolism)</term><term>Insulin-Secreting Cells (metabolism)</term><term>Lactic Acid (blood)</term><term>Magnetic Resonance Imaging</term><term>Mass Spectrometry</term><term>Mice</term><term>Mice, Knockout</term><term>Muscle, Skeletal (metabolism)</term><term>Polymerase Chain Reaction</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide lactique (sang)</term><term>Animaux</term><term>Cellules à insuline (métabolisme)</term><term>Cholestérol (métabolisme)</term><term>Fatty acid synthases</term><term>Glucose (métabolisme)</term><term>Glycogène (métabolisme)</term><term>Homéostasie (génétique)</term><term>Homéostasie (physiologie)</term><term>Imagerie par résonance magnétique</term><term>Insuline (métabolisme)</term><term>Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP (déficit)</term><term>Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP (métabolisme)</term><term>Muscles squelettiques (métabolisme)</term><term>Réaction de polymérisation en chaîne</term><term>Souris</term><term>Souris knockout</term><term>Spectrométrie de masse</term><term>Technique de Western</term><term>Tissu adipeux (métabolisme)</term><term>Transporteur-1 à cassette liant l'ATP (déficit)</term><term>Transporteur-1 à cassette liant l'ATP (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Lactic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>ATP Binding Cassette Transporter 1</term><term>ATP Binding Cassette Transporter, Sub-Family G, Member 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ATP Binding Cassette Transporter 1</term><term>ATP Binding Cassette Transporter, Sub-Family G, Member 1</term><term>Cholesterol</term><term>Glucose</term><term>Glycogen</term><term>Insulin</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP</term><term>Transporteur-1 à cassette liant l'ATP</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Homeostasis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Homéostasie</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adipose Tissue</term><term>Insulin-Secreting Cells</term><term>Muscle, Skeletal</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules à insuline</term><term>Cholestérol</term><term>Glucose</term><term>Glycogène</term><term>Insuline</term><term>Membre-1 de la sous-famille G des transporteurs à cassette liant l'ATP</term><term>Muscles squelettiques</term><term>Tissu adipeux</term><term>Transporteur-1 à cassette liant l'ATP</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Homéostasie</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Homeostasis</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Acide lactique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Fatty Acid Synthases</term><term>Magnetic Resonance Imaging</term><term>Mass Spectrometry</term><term>Mice</term><term>Mice, Knockout</term><term>Polymerase Chain Reaction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Fatty acid synthases</term><term>Imagerie par résonance magnétique</term><term>Réaction de polymérisation en chaîne</term><term>Souris</term><term>Souris knockout</term><term>Spectrométrie de masse</term><term>Technique de Western</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>États-Unis</li></country><region><li>Nouvelle-Galles du Sud</li><li>Provence-Alpes-Côte d'Azur</li><li>État de New York</li></region><settlement><li>Marseille</li><li>Sydney</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Cochran, Blake J" sort="Cochran, Blake J" uniqKey="Cochran B" first="Blake J" last="Cochran">Blake J. Cochran</name></region><name sortKey="Barter, Philip J" sort="Barter, Philip J" uniqKey="Barter P" first="Philip J" last="Barter">Philip J. Barter</name><name sortKey="Bongers, Andre" sort="Bongers, Andre" uniqKey="Bongers A" first="Andre" last="Bongers">Andre Bongers</name><name sortKey="Cuesta Torres, Luisa" sort="Cuesta Torres, Luisa" uniqKey="Cuesta Torres L" first="Luisa" last="Cuesta Torres">Luisa Cuesta Torres</name><name sortKey="Hou, Liming" sort="Hou, Liming" uniqKey="Hou L" first="Liming" last="Hou">Liming Hou</name><name sortKey="Manavalan, Anil Paul Chirackal" sort="Manavalan, Anil Paul Chirackal" uniqKey="Manavalan A" first="Anil Paul Chirackal" last="Manavalan">Anil Paul Chirackal Manavalan</name><name sortKey="Moore, Benjamin M" sort="Moore, Benjamin M" uniqKey="Moore B" first="Benjamin M" last="Moore">Benjamin M. Moore</name><name sortKey="Patel, Mili" sort="Patel, Mili" uniqKey="Patel M" first="Mili" last="Patel">Mili Patel</name><name sortKey="Ryder, William J" sort="Ryder, William J" uniqKey="Ryder W" first="William J" last="Ryder">William J. Ryder</name><name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name><name sortKey="Senanayake, Praween" sort="Senanayake, Praween" uniqKey="Senanayake P" first="Praween" last="Senanayake">Praween Senanayake</name><name sortKey="Shrestha, Sudichhya" sort="Shrestha, Sudichhya" uniqKey="Shrestha S" first="Sudichhya" last="Shrestha">Sudichhya Shrestha</name><name sortKey="Sultana, Afroza" sort="Sultana, Afroza" uniqKey="Sultana A" first="Afroza" last="Sultana">Afroza Sultana</name><name sortKey="Tabet, Fatiha" sort="Tabet, Fatiha" uniqKey="Tabet F" first="Fatiha" last="Tabet">Fatiha Tabet</name><name sortKey="Tang, Shudi" sort="Tang, Shudi" uniqKey="Tang S" first="Shudi" last="Tang">Shudi Tang</name><name sortKey="Wasinger, Valerie C" sort="Wasinger, Valerie C" uniqKey="Wasinger V" first="Valerie C" last="Wasinger">Valerie C. Wasinger</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Maraninchi, Marie" sort="Maraninchi, Marie" uniqKey="Maraninchi M" first="Marie" last="Maraninchi">Marie Maraninchi</name></region></country><country name="États-Unis"><region name="État de New York"><name sortKey="Westerterp, Marit" sort="Westerterp, Marit" uniqKey="Westerterp M" first="Marit" last="Westerterp">Marit Westerterp</name></region><name sortKey="Tall, Alan R" sort="Tall, Alan R" uniqKey="Tall A" first="Alan R" last="Tall">Alan R. Tall</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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