Forskning ved Københavns Universitet - Københavns Universitet

Forside

Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Elisa Vergari
  • Knudsen, Jakob Grunnet
  • Reshma Ramracheya
  • Albert Salehi
  • Quan Zhang
  • Julie Adam
  • Ingrid Wernstedt Asterholm
  • Anna Benrick
  • Linford J B Briant
  • Margarita V Chibalina
  • Fiona M Gribble
  • Alexander Hamilton
  • Benoit Hastoy
  • Frank Reimann
  • Nils J G Rorsman
  • Ioannis I Spiliotis
  • Andrei Tarasov
  • Yanling Wu
  • Frances M Ashcroft
  • Patrik Rorsman

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.

OriginalsprogEngelsk
Artikelnummer139
TidsskriftNature Communications
Vol/bind10
Antal sider11
ISSN2041-1723
DOI
StatusUdgivet - 2019
Eksternt udgivetJa

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 220850488