β Cell-Specific Deletion of the IL-1 Receptor Antagonist Impairs β Cell Proliferation and Insulin Secretion.
- Böni-Schnetzler M Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland. Electronic address: marianne.boeni@unibas.ch.
- Häuselmann SP Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Dalmas E Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Meier DT Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Thienel C Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Traub S Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Schulze F Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Steiger L Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Dror E Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- Martin P Department of Pathology and Immunology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
- Herrera PL Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211 Geneva, Switzerland; Centre Facultaire du Diabète, University of Geneva, 1211 Geneva, Switzerland.
- Gabay C Department of Pathology and Immunology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
- Donath MY Department of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
- 2018-02-15
Published in:
- Cell reports. - 2018
ATP-sensitive K+ channel subunit Kir6.2
E2F1 transcription factor
IL-1 receptor antagonist
diabetes
glucose-stimulated insulin secretion
interleukin-1β
islet β cells
β cell proliferation
Animals
Biomarkers
Cell Proliferation
E2F1 Transcription Factor
Gene Deletion
Glucose
Glucose Intolerance
Insulin Secretion
Insulin-Secreting Cells
Interleukin 1 Receptor Antagonist Protein
Male
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Myeloid Cells
Obesity
Organ Specificity
English
Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in β cells, but not in myeloid cells, resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main source of circulating IL-1Ra in obesity. βIL-1Ra KO mice had impaired insulin secretion, reduced β cell proliferation, and decreased expression of islet proliferation genes, along with impaired glucose tolerance. The key cell-cycle regulator E2F1 partly reversed IL-1β-mediated inhibition of potassium channel Kir6.2 expression and rescued impaired insulin secretion in IL-1Ra knockout islets. Our findings provide evidence for the importance of β cell-derived IL-1Ra for the local defense of β cells to maintain normal function and proliferation.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.celrep.2018.01.063
- PMID 29444430
- Persistent URL
- https://sonar.ch/global/documents/213730
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