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 reducesIns2expression 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.

中文翻译：

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Artemether不会将α细胞转变为β细胞

胰腺α细胞保留相当大的可塑性，并且在适当的情况下可以转分化为功能成熟的β细胞。为了寻找可作为目标的机制，最近的一篇论文提出，广泛使用的抗疟疾药物蒿甲醚可抑制α细胞转录因子Arx从而促进转分化为β细胞。但是，本文的关键初始实验是在胰岛细胞系中进行的，大多数后续验证实验都暗示了转分化作用，而没有直接证明α向β细胞的转化。确实，我们没有发现证据表明蒿甲醚能促进原代α细胞向β细胞的转分化。此外，蒿甲醚可降低> 100倍的原代β细胞中Ins2的表达，抑制葡萄糖的摄取，并消除葡萄糖对β细胞的钙反应和胰岛素分泌。我们的观察结果表明，蒿甲醚可诱导一般的胰岛内分泌细胞去分化，并质疑青蒿素在促进糖尿病中从α到β细胞转分化的效用。