dc.contributor.author | Vergari, Elisa | |
dc.contributor.author | Knudsen, Jakob G | |
dc.contributor.author | Ramracheya, Reshma | |
dc.contributor.author | Salehi, Albert | |
dc.contributor.author | Zhang, Quan | |
dc.contributor.author | Adam, Julie | |
dc.contributor.author | Asterholm, Ingrid Wernstedt | |
dc.contributor.author | Benrick, Anna | |
dc.contributor.author | Briant, Linford J B | |
dc.contributor.author | Chibalina, Margarita V | |
dc.contributor.author | Gribble, Fiona M | |
dc.contributor.author | Hamilton, Alexander | |
dc.contributor.author | Hastoy, Benoit | |
dc.contributor.author | Reimann, Frank | |
dc.contributor.author | Rorsman, Nils J G | |
dc.contributor.author | Spiliotis, Ioannis I | |
dc.contributor.author | Tarasov, Andrei | |
dc.contributor.author | Wu, Yanling | |
dc.contributor.author | Ashcroft, Frances M | |
dc.contributor.author | Rorsman, Patrik | |
dc.date.accessioned | 2019-03-05T11:19:45Z | |
dc.date.available | 2019-03-05T11:19:45Z | |
dc.date.issued | 2019-01-11 | |
dc.identifier.citation | Vergari , 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.issn | 2041-1723 | |
dc.identifier.other | ORCID: /0000-0002-8883-176X/work/62751484 | |
dc.identifier.uri | http://hdl.handle.net/2299/21167 | |
dc.description | © The Author(s) 2019 | |
dc.description.abstract | Hypoglycaemia (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.extent | 1 | |
dc.format.extent | 1008434 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | |
dc.subject | General Chemistry | |
dc.subject | General Biochemistry,Genetics and Molecular Biology | |
dc.subject | General Physics and Astronomy | |
dc.title | Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion | en |
dc.contributor.institution | Extracellular Vesicle Research Unit | |
dc.contributor.institution | Department of Biological and Environmental Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.description.status | Peer reviewed | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85059897193&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.1038/s41467-018-08193-8 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |