{"entity": "researcher", "timestamp": "2026-09-29T21:51:54.130Z", "family": "Alonso", "given": "Laura C", "initials": "LC", "orcid": "0000-0001-5056-8970", "affiliations": ["Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, New York, NY, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e06c04e0634944aebe80c1a5e7d149bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e06c04e0634944aebe80c1a5e7d149bd"}}, "publications": [{"entity": "publication", "iuid": "cd29995ce54f4787aa0760c7d943ea71", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cd29995ce54f4787aa0760c7d943ea71.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cd29995ce54f4787aa0760c7d943ea71"}}, "title": "In vivo screen identifies a SIK inhibitor that induces \u03b2 cell proliferation through a transient UPR.", "authors": [{"family": "Charbord", "given": "J\u00e9r\u00e9mie", "initials": "J", "orcid": "0000-0002-8411-8182", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c074fcfc61e343b28cb43741f778c768.json"}}, {"family": "Ren", "given": "Lipeng", "initials": "L"}, {"family": "Sharma", "given": "Rohit B", "initials": "RB"}, {"family": "Johansson", "given": "Anna", "initials": "A"}, {"family": "\u00c5gren", "given": "Rasmus", "initials": "R"}, {"family": "Chu", "given": "Lianhe", "initials": "L"}, {"family": "Tworus", "given": "Dominika", "initials": "D"}, {"family": "Schulz", "given": "Nadja", "initials": "N"}, {"family": "Charbord", "given": "Pierre", "initials": "P"}, {"family": "Stewart", "given": "Andrew F", "initials": "AF", "orcid": "0000-0001-7866-5959", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a66b111b62554c81a188a2fc31c9c3e8.json"}}, {"family": "Wang", "given": "Peng", "initials": "P"}, {"family": "Alonso", "given": "Laura C", "initials": "LC", "orcid": "0000-0001-5056-8970", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e06c04e0634944aebe80c1a5e7d149bd.json"}}, {"family": "Andersson", "given": "Olov", "initials": "O", "orcid": "0000-0001-6715-781X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2f39763e006e48309fc287cdb644ffe4.json"}}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "3", "issue": "5", "pages": "682-700", "issn-l": "2522-5812"}, "abstract": "It is known that \u03b2 cell proliferation expands the \u03b2 cell mass during development and under certain hyperglycemic conditions in the adult, a process that may be used for \u03b2 cell regeneration in diabetes. Here, through a new high-throughput screen using a luminescence ubiquitination-based cell cycle indicator (LUCCI) in zebrafish, we identify HG-9-91-01 as a driver of proliferation and confirm this effect in mouse and human \u03b2 cells. HG-9-91-01 is an inhibitor of salt-inducible kinases (SIKs), and overexpression of Sik1 specifically in \u03b2 cells blocks the effect of HG-9-91-01 on \u03b2 cell proliferation. Single-cell transcriptomic analyses of mouse \u03b2 cells demonstrate that HG-9-91-01 induces a wave of activating transcription factor (ATF)6-dependent unfolded protein response (UPR) before cell cycle entry. Importantly, the UPR wave is not associated with an increase in insulin expression. Additional mechanistic studies indicate that HG-9-91-01 induces multiple signalling effectors downstream of SIK inhibition, including CRTC1, CRTC2, ATF6, IRE1 and mTOR, which integrate to collectively drive \u03b2 cell proliferation.", "doi": "10.1038/s42255-021-00391-x", "pmid": "34031592", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1854461"}, {"db": "pmc", "key": "PMC9756392"}, {"db": "pii", "key": "10.1038/s42255-021-00391-x"}], "notes": [], "created": "2026-09-23T09:44:43.284Z", "modified": "2026-09-23T10:18:58.919Z"}]}