{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jia J"],"funding":["Natural Science Foundation of Fujian Province","Natural Science Foundation of Fujian Province (Fujian Provincial Natural Science Foundation)"],"pagination":["2473"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11903786"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Blockade of the glucagon receptor (GCGR) has been shown to improve glycemic control. However, this therapeutic approach also brings side effects, such as α-cell hyperplasia and hyperglucagonemia, and the mechanisms underlying these side effects remain elusive. Here, we conduct single-cell transcriptomic sequencing of islets from male GCGR knockout (GCGR-KO) mice. Our analysis confirms the elevated expression of Gcg in GCGR-KO mice, along with enhanced glucagon secretion at single-cell level. Notably, Vgf (nerve growth factor inducible) is specifically upregulated in α cells of GCGR-KO mice. Inhibition of VGF impairs the formation of glucagon immature secretory granules and compromises glucagon maturation, lead to reduced α-cell hypersecretion of glucagon. We further demonstrate that activa"],"journal":["Nature communications"],"pubmed_title":["Blockade of glucagon receptor induces α-cell hypersecretion by hyperaminoacidemia in mice."],"pmcid":["PMC11903786"],"funding_grant_id":["2023I0002"],"pubmed_authors":["Jin Q","Kang Q","Jiang F","Wong FS","Bai X","Li M","Jia J"],"additional_accession":[]},"is_claimable":false,"name":"Blockade of glucagon receptor induces α-cell hypersecretion by hyperaminoacidemia in mice.","description":"Blockade of the glucagon receptor (GCGR) has been shown to improve glycemic control. However, this therapeutic approach also brings side effects, such as α-cell hyperplasia and hyperglucagonemia, and the mechanisms underlying these side effects remain elusive. Here, we conduct single-cell transcriptomic sequencing of islets from male GCGR knockout (GCGR-KO) mice. Our analysis confirms the elevated expression of Gcg in GCGR-KO mice, along with enhanced glucagon secretion at single-cell level. Notably, Vgf (nerve growth factor inducible) is specifically upregulated in α cells of GCGR-KO mice. Inhibition of VGF impairs the formation of glucagon immature secretory granules and compromises glucagon maturation, lead to reduced α-cell hypersecretion of glucagon. We further demonstrate that activa","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-04-21T16:55:03.162Z","creation":"2025-04-21T16:55:03.162Z"},"accession":"S-EPMC11903786","cross_references":{"pubmed":["40075066"],"doi":["10.1038/s41467-025-57786-7"]}}