دورية أكاديمية
ABCA12 regulates insulin secretion from β-cells.
| العنوان: | ABCA12 regulates insulin secretion from β-cells. |
|---|---|
| المؤلفون: | Ursino GM; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Fu Y; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Cottle DL; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Mukhamedova N; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Jones LK; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Low H; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Tham MS; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Gan WJ; Charles Perkins Centre, Camperdown, NSW, Australia., Mellett NA; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Das PP; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Weir JM; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Ditiatkovski M; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Fynch S; St Vincent's Institute, Fitzroy, Vic., Australia., Thorn P; Charles Perkins Centre, Camperdown, NSW, Australia., Thomas HE; St Vincent's Institute, Fitzroy, Vic., Australia., Meikle PJ; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia., Parkington HC; Department of Physiology, Neuroscience Discovery Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Smyth IM; Department of Anatomy and Developmental Biology, Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Sviridov D; Baker Heart and Diabetes Institute, Melbourne, Vic., Australia. |
| المصدر: | EMBO reports [EMBO Rep] 2020 Mar 04; Vol. 21 (3), pp. e48692. Date of Electronic Publication: 2020 Feb 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000- |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2*/metabolism , Insulin-Secreting Cells*/metabolism, ATP Binding Cassette Transporter 1/genetics ; ATP Binding Cassette Transporter 1/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Animals ; Glucose/metabolism ; Insulin/metabolism ; Insulin Secretion ; Mice |
| مستخلص: | Dysregulation of lipid homeostasis is intimately associated with defects in insulin secretion, a key feature of type 2 diabetes. Here, we explore the role of the putative lipid transporter ABCA12 in regulating insulin secretion from β-cells. Mice with β-cell-specific deletion of Abca12 display impaired glucose-stimulated insulin secretion and eventual islet inflammation and β-cell death. ABCA12's action in the pancreas is independent of changes in the abundance of two other cholesterol transporters, ABCA1 and ABCG1, or of changes in cellular cholesterol or ceramide content. Instead, loss of ABCA12 results in defects in the genesis and fusion of insulin secretory granules and increases in the abundance of lipid rafts at the cell membrane. These changes are associated with dysregulation of the small GTPase CDC42 and with decreased actin polymerisation. Our findings establish a new, pleiotropic role for ABCA12 in regulating pancreatic lipid homeostasis and insulin secretion. (© 2020 The Authors.) |
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| معلومات مُعتمدة: | APP1123554 International Department of Health | National Health and Medical Research Council (NHMRC); APP1020281 International Department of Health | National Health and Medical Research Council (NHMRC); APP1036352 International Department of Health | National Health and Medical Research Council (NHMRC); APP1106516 International Department of Health | National Health and Medical Research Council (NHMRC); GNT1020281 International Department of Health | National Health and Medical Research Council (NHMRC); GNT1036352 International Department of Health | National Health and Medical Research Council (NHMRC); GNT1123554 International Department of Health | National Health and Medical Research Council (NHMRC) |
| فهرسة مساهمة: | Keywords: ABCA12; cholesterol homeostasis; insulin secretion; lipid rafts; type 2 diabetes |
| سلسلة جزيئية: | GEO GSE140379 |
| المشرفين على المادة: | 0 (ATP Binding Cassette Transporter 1) 0 (ATP-Binding Cassette Transporters) 0 (Abca12 protein, mouse) 0 (Insulin) IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20200220 Date Completed: 20210427 Latest Revision: 20220531 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7054684 |
| DOI: | 10.15252/embr.201948692 |
| PMID: | 32072744 |
| قاعدة البيانات: | MEDLINE |
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