Artemether Does Not Turn α Cells into β Cells

• DOI: 10.1016/j.cmet.2017.10.002
• Publication Date: 2017-11-02T16:58:00Z
• Authors: Talitha van der M...; Sharon Lee; Els Noordeloos; Cynthia J. Donaldson; Michael W. Adams; Glyn M. Noguchi; Alex M. Mawla; Mark O. Huising
• Keywords: 570; transdifferentiation; Cells; 610; artemether; GCaMP6; Medical Biochemistry and Metabolomics; Inbred C57BL; Mice; Endocrinology & Metabolism; 03 medical and health sciences; Insulin-Secreting Cells; Insulin Secretion; Medical biochemistry and metabolomics; Animals; Insulin; artemisinins; Metabolic and endocrine; Cells, Cultured; Homeodomain Proteins; 0303 health sciences; Cultured; diabetes; Cell Death; maturation; Diabetes; dedifferentiation; Biological Sciences; pancreatic islet; 3. Good health; Mice, Inbred C57BL; Good Health and Well Being; Glucose; Glucagon-Secreting Cells; Biochemistry and cell biology; Cell Transdifferentiation; Calcium; Biochemistry and Cell Biology; Artemether; neogenesis; Transcription Factors

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.