Abstract:
:Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. By RNA sequencing of human EECs purified by flow cytometry after cell fixation and staining, we present a first transcriptomic analysis of human EEC populations and demonstrate a strong correlation with murine counterparts. RNA sequencing was deep enough to enable identification of low-abundance transcripts such as G-protein-coupled receptors and ion channels, revealing expression in human EECs of G-protein-coupled receptors previously found to play roles in postprandial nutrient detection. With liquid chromatography-tandem mass spectrometry, we profiled the gradients of peptide hormones along the human and mouse gut, including their sequences and posttranslational modifications. The transcriptomic and peptidomic profiles of human and mouse EECs and cross-species comparison will be valuable tools for drug discovery programs and for understanding human metabolism and the endocrine impacts of bariatric surgery.
journal_name
Diabetesjournal_title
Diabetesauthors
Roberts GP,Larraufie P,Richards P,Kay RG,Galvin SG,Miedzybrodzka EL,Leiter A,Li HJ,Glass LL,Ma MKL,Lam B,Yeo GSH,Scharfmann R,Chiarugi D,Hardwick RH,Reimann F,Gribble FMdoi
10.2337/db18-0883subject
Has Abstractpub_date
2019-05-01 00:00:00pages
1062-1072issue
5eissn
0012-1797issn
1939-327Xpii
db18-0883journal_volume
68pub_type
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