Artemether Does Not Turn α Cells into β Cells

Talitha van der Meulen, Sharon Lee, Els Noordeloos, Cynthia J. Donaldson, Michael W. Adams, Glyn M. Noguchi, Alex M. Mawla, Mark O. Huising

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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. The anti-malaria drug artemether has been recently shown to promote transdifferentiation of α cells into β cells. Instead, van der Meulen et al. now report loss of β cell gene expression, glucose uptake, calcium responses, and insulin secretion following stimulation in intact islets treated with the same high dose of artemether.

Original languageEnglish (US)
Pages (from-to)218-225.e4
JournalCell Metabolism
Volume27
Issue number1
DOIs
StatePublished - Jan 9 2018

Keywords

  • artemether
  • artemisinins
  • dedifferentiation
  • diabetes
  • GCaMP6
  • maturation
  • neogenesis
  • pancreatic islet
  • transdifferentiation

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Artemether Does Not Turn α Cells into β Cells'. Together they form a unique fingerprint.

Cite this