دورية أكاديمية

Pancreatic deletion of the interleukin-1 receptor disrupts whole body glucose homeostasis and promotes islet β-cell de-differentiation

التفاصيل البيبلوغرافية
العنوان: Pancreatic deletion of the interleukin-1 receptor disrupts whole body glucose homeostasis and promotes islet β-cell de-differentiation
المؤلفون: Susan J. Burke, Heidi M. Batdorf, David H. Burk, Thomas M. Martin, Tamra Mendoza, Krisztian Stadler, Wateen Alami, Michael D. Karlstad, Matthew J. Robson, Randy D. Blakely, Randall L. Mynatt, J. Jason Collier
المصدر: Molecular Metabolism, Vol 14, Iss , Pp 95-107 (2018)
بيانات النشر: Elsevier, 2018.
سنة النشر: 2018
المجموعة: LCC:Internal medicine
مصطلحات موضوعية: Internal medicine, RC31-1245
الوصف: Objective: Pancreatic tissue, and islets in particular, are enriched in expression of the interleukin-1 receptor type I (IL-1R). Because of this enrichment, islet β-cells are exquisitely sensitive to the IL-1R ligands IL-1α and IL-1β, suggesting that signaling through this pathway regulates health and function of islet β-cells. Methods: Herein, we report a targeted deletion of IL-1R in pancreatic tissue (IL-1RPdx1−/−) in C57BL/6J mice and in db/db mice on the C57 genetic background. Islet morphology, β-cell transcription factor abundance, and expression of the de-differentiation marker Aldh1a3 were analyzed by immunofluorescent staining. Glucose and insulin tolerance tests were used to examine metabolic status of these genetic manipulations. Glucose-stimulated insulin secretion was evaluated in vivo and in isolated islets ex vivo by perifusion. Results: Pancreatic deletion of IL-1R leads to impaired glucose tolerance, a phenotype that is exacerbated by age. Crossing the IL-1RPdx1−/− with db/db mice worsened glucose tolerance without altering body weight. There were no detectable alterations in insulin tolerance between IL-1RPdx1−/− mice and littermate controls. However, glucose-stimulated insulin secretion was reduced in islets isolated from IL-1RPdx1−/− relative to control islets. Insulin output in vivo after a glucose challenge was also markedly reduced in IL-1RPdx1−/− mice when compared with littermate controls. Pancreatic islets from IL-1RPdx1−/− mice displayed elevations in Aldh1a3, a marker of de-differentiation, and reduction in nuclear abundance of the β-cell transcription factor MafA. Nkx6.1 abundance was unaltered. Conclusions: There is an important physiological role for pancreatic IL-1R to promote glucose homeostasis by suppressing expression of Aldh1a3, sustaining MafA abundance, and supporting glucose-stimulated insulin secretion in vivo. Keywords: Cytokine, Glucose homeostasis, Inflammation, Insulin, Islet
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2212-8778
Relation: http://www.sciencedirect.com/science/article/pii/S2212877818303041; https://doaj.org/toc/2212-8778
DOI: 10.1016/j.molmet.2018.06.003
URL الوصول: https://doaj.org/article/3e446786db4e433f84a292436eed3c59
رقم الأكسشن: edsdoj.3e446786db4e433f84a292436eed3c59
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22128778
DOI:10.1016/j.molmet.2018.06.003