دورية أكاديمية
أعرض في EDS

Direct suppression of human islet dedifferentiation, progenitor genes, but not epithelial to mesenchymal transition by liraglutide.

التفاصيل البيبلوغرافية
العنوان: Direct suppression of human islet dedifferentiation, progenitor genes, but not epithelial to mesenchymal transition by liraglutide.
المؤلفون: Rattanaamnuaychai P; School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand., Roshorm YM; School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand., Wilasrusmee C; Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Proprom N; Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Ongphiphadhanakul B; Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Talchai SC; Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand.; Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok, Thailand.
المصدر: Heliyon [Heliyon] 2020 Sep 15; Vol. 6 (9), pp. e04951. Date of Electronic Publication: 2020 Sep 15 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101672560 Publication Model: eCollection Cited Medium: Print ISSN: 2405-8440 (Print) Linking ISSN: 24058440 NLM ISO Abbreviation: Heliyon Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: London : Elsevier Ltd, [2015]-
مستخلص: β-cell dedifferentiation has been accounted as one of the major mechanisms for β-cell failure; thus, is a cause to diabetes. We study direct impacts of liraglutide treatment on ex vivo human dedifferentiated islets, and its effects on genes important in endocrine function, progenitor states, and epithelial mesenchymal transition (EMT). Human islets from non-diabetic donors, were purified and incubated until day 1 and day 4, and were determined insulin contents, numbers of insulin (INS + ) and glucagon (GCG + ) cells. The islets from day 3 to day 7 were treated with diabetic drugs, the long acting GLP-1 receptor agonist, liraglutide. As observed in pancreatic islets of type 2 diabetic patients, ex vivo dedifferentiated islets showed more than 50% reduced insulin contents while number of glucagon increased from 10% to about 20%. β-cell specific genes: PDX1 , MAFA , as well as β-cell functional markers: GLUT1 and SUR1, were significantly depleted more than 40%. Notably, we found increased levels of glucagon regulator, ARX and pre-glucagon transcripts, and remarkably upregulated progenitor expressions: NEUROG3 and ALDH1A identified as β-cell dysfunction markers in diabetic models. Hyperglucagonemia was often observed in type 2 patients that could lead to over production of gluconeogenesis by the liver. Liraglutide treatments resulted in decreased number of GCG + cells, increased numbers of GLP-1 positive cells but did not alter elevated levels of EMT marker genes: ACTA2, CDH-2, SNAIL2, and VIM . These effects of liraglutide were blunted when FOXO1 transcripts were depleted. This work illustrates that ex vivo human isolated islets can be used as a tool to study different aspects of β-cell dedifferentiation. Our novel finding suggests a role of GLP-1 pathway in beta-cell maintenance in FOXO1-dependent manner. Importantly, dedifferentiated islets ex vivo is a useful model that can be utilized to verify the actions of potential drugs to diabetic β-cell failure.
(© 2020 The Authors.)
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فهرسة مساهمة: Keywords: Cell biology; Dedifferentiation; Diabetes; Endocrinology; FOXO1; Gastrointestinal system; Glucagon; Isolated islets; Liraglutide; Molecular biology; β−cell
تواريخ الأحداث: Date Created: 20200930 Latest Revision: 20201002
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7501427
DOI: 10.1016/j.heliyon.2020.e04951
PMID: 32995630
قاعدة البيانات: MEDLINE
الوصف
تدمد:2405-8440
DOI:10.1016/j.heliyon.2020.e04951