دورية أكاديمية
Artemether Does Not Turn α Cells into β Cells.
العنوان: | Artemether Does Not Turn α Cells into β Cells. |
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المؤلفون: | van der Meulen T; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Lee S; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Noordeloos E; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Donaldson CJ; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Adams MW; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Noguchi GM; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Mawla AM; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA., Huising MO; Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA 95616, USA. Electronic address: mhuising@ucdavis.edu. |
المصدر: | Cell metabolism [Cell Metab] 2018 Jan 09; Vol. 27 (1), pp. 218-225.e4. Date of Electronic Publication: 2017 Nov 02. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2005- |
مواضيع طبية MeSH: | Artemether/*pharmacology , Glucagon-Secreting Cells/*metabolism , Insulin-Secreting Cells/*metabolism, Animals ; Calcium/metabolism ; Cell Death/drug effects ; Cell Transdifferentiation ; Cells, Cultured ; Glucagon-Secreting Cells/drug effects ; Glucose/metabolism ; Homeodomain Proteins/metabolism ; Insulin/metabolism ; Insulin Secretion/drug effects ; Insulin-Secreting Cells/drug effects ; Mice, Inbred C57BL ; Transcription Factors/metabolism |
مستخلص: | Pancreatic α cells retain considerable plasticity and can, under the right circumstances, transdifferentiate into functionally mature β cells. In search of a targetable mechanistic basis, a recent paper suggested that the widely used anti-malaria drug artemether suppresses the α cell transcription factor Arx to promote transdifferentiation into β cells. However, key initial experiments in this paper were carried out in islet cell lines, and most subsequent validation experiments implied transdifferentiation without direct demonstration of α to β cell conversion. Indeed, we find no evidence that artemether promotes transdifferentiation of primary α cells into β cells. Moreover, artemether reduces Ins2 expression in primary β cells >100-fold, suppresses glucose uptake, and abrogates β cell calcium responses and insulin secretion in response to glucose. Our observations suggest that artemether induces general islet endocrine cell dedifferentiation and call into question the utility of artemisinins to promote α to β cell transdifferentiation in treating diabetes. (Copyright © 2017 Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | T32 GM007377 United States GM NIGMS NIH HHS; T32 GM099608 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: GCaMP6; artemether; artemisinins; dedifferentiation; diabetes; maturation; neogenesis; pancreatic islet; transdifferentiation |
المشرفين على المادة: | 0 (ARX protein, mouse) 0 (Homeodomain Proteins) 0 (Insulin) 0 (Transcription Factors) C7D6T3H22J (Artemether) IY9XDZ35W2 (Glucose) SY7Q814VUP (Calcium) |
تواريخ الأحداث: | Date Created: 20171107 Date Completed: 20190527 Latest Revision: 20210109 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5762275 |
DOI: | 10.1016/j.cmet.2017.10.002 |
PMID: | 29103923 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1932-7420 |
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DOI: | 10.1016/j.cmet.2017.10.002 |