Furin controls β cell function via mTORC1 signaling
作者： Bas Brouwers , Ilaria Coppola , Katlijn Vints , Bastian Dislich , Nathalie Jouvet
DOI: 10.1101/2020.04.09.027839
关键词:
摘要: Furin is a proprotein convertase (PC) responsible for proteolytic activation of wide array precursor proteins within the secretory pathway. It maps to PRC1 locus, type 2 diabetes susceptibility yet its specific role in pancreatic β cells largely unknown. The aim this study was determine furin glucose homeostasis. We show that highly expressed human islets, while PCs potentially could provide redundancy are at considerably lower levels. cell-specific knockout (βfurKO) mice intolerant, due smaller islets with insulin content and abnormal dense core granule morphology. RNA expression analysis differential proteomics on βfurKO revealed Activating Transcription Factor 4 (ATF4), which mediated by mammalian target rapamycin C1 (mTORC1). impaired cleavage essential V-ATPase subunit Ac45, blocking pump mTORC1 pathway activated. Furthermore, lack receptor response insulin. Taken together, these results suggest model mTORC1-ATF4 hyperactivation lacking furin, causes cell dysfunction.
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