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dc.contributor.authorVergari, Elisa
dc.contributor.authorKnudsen, Jakob G
dc.contributor.authorRamracheya, Reshma
dc.contributor.authorSalehi, Albert
dc.contributor.authorZhang, Quan
dc.contributor.authorAdam, Julie
dc.contributor.authorAsterholm, Ingrid Wernstedt
dc.contributor.authorBenrick, Anna
dc.contributor.authorBriant, Linford J B
dc.contributor.authorChibalina, Margarita V
dc.contributor.authorGribble, Fiona M
dc.contributor.authorHamilton, Alexander
dc.contributor.authorHastoy, Benoit
dc.contributor.authorReimann, Frank
dc.contributor.authorRorsman, Nils J G
dc.contributor.authorSpiliotis, Ioannis I
dc.contributor.authorTarasov, Andrei
dc.contributor.authorWu, Yanling
dc.contributor.authorAshcroft, Frances M
dc.contributor.authorRorsman, Patrik
dc.date.accessioned2019-03-05T11:19:45Z
dc.date.available2019-03-05T11:19:45Z
dc.date.issued2019-01-11
dc.identifier.citationVergari , E , Knudsen , J G , Ramracheya , R , Salehi , A , Zhang , Q , Adam , J , Asterholm , I W , Benrick , A , Briant , L J B , Chibalina , M V , Gribble , F M , Hamilton , A , Hastoy , B , Reimann , F , Rorsman , N J G , Spiliotis , I I , Tarasov , A , Wu , Y , Ashcroft , F M & Rorsman , P 2019 , ' Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion ' , Nature Communications , vol. 10 , no. 1 , 139 , pp. 139 . https://doi.org/10.1038/s41467-018-08193-8
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 16120242
dc.identifier.otherPURE UUID: 3ef30850-5981-46bb-bd5a-ad32f267a036
dc.identifier.otherPubMed: 30635569
dc.identifier.otherScopus: 85059897193
dc.identifier.urihttp://hdl.handle.net/2299/21167
dc.description© The Author(s) 2019
dc.description.abstractHypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin's capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin's hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy.en
dc.format.extent1
dc.language.isoeng
dc.relation.ispartofNature Communications
dc.rightsOpen
dc.subjectChemistry(all)
dc.subjectBiochemistry, Genetics and Molecular Biology(all)
dc.subjectPhysics and Astronomy(all)
dc.titleInsulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretionen
dc.contributor.institutionExtracellular Vesicle Research Unit
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85059897193&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2019-01-11
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1038/s41467-018-08193-8
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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