AIMS/HYPOTHESIS: Somatostatin (SST) released from islet δ-cells inhibits both insulin and glucagon secretion but the role of this tonic inhibition is unclear. In this study we investigated whether δ-cell SST may facilitate sympathetic regulation of glucagon secretion as part of an 'accelerator/brake' mechanism. METHODS: The secretory characteristics of islets isolated from SST-deficient (Sst-/-) and control mouse islets were assessed in static incubation studies. Glucagon and SST release was measured by radioimmunoassay (RIA). RESULTS: Arginine stimulated both glucagon and SST release from control mouse islets whereas the sympathetic neurotransmitter noradrenaline (NA) increased glucagon secretion but inhibited SST release in the presence of 2 mmol/l glucose or 20 mmol/l arginine. Experiments were performed using Sst-/- islets to assess whether the reduction of SST secretion by NA offers an indirect mechanism of enhancing glucagon release in response to sympathetic activation. Arginine-induced but not NA-induced glucagon release from Sst-/- islets was significantly increased compared to controls. In combination, NA enhanced arginine-induced release from both groups of mouse islets but to a greater extent in control islets, leading to similar overall levels of glucagon release. The responsiveness of Sst-/- islets to NA was thus blunted under stimulatory but not sub-stimulatory conditions of SST release. CONCLUSIONS: Our data suggest that sympathetic activation of glucagon release may be partly mediated by an indirect effect on SST secretion, where the tonic inhibition by δ-cell SST on α-cells is removed, facilitating precise and substantial changes in glucagon release in response to NA.
AIMS/HYPOTHESIS: Somatostatin (SST) released from islet δ-cells inhibits both insulin and glucagon secretion but the role of this tonic inhibition is unclear. In this study we investigated whether δ-cell SST may facilitate sympathetic regulation of glucagon secretion as part of an 'accelerator/brake' mechanism. METHODS: The secretory characteristics of islets isolated from SST-deficient (Sst-/-) and control mouse islets were assessed in static incubation studies. Glucagon and SST release was measured by radioimmunoassay (RIA). RESULTS:Arginine stimulated both glucagon and SST release from control mouse islets whereas the sympathetic neurotransmitter noradrenaline (NA) increased glucagon secretion but inhibited SST release in the presence of 2 mmol/l glucose or 20 mmol/l arginine. Experiments were performed using Sst-/- islets to assess whether the reduction of SST secretion by NA offers an indirect mechanism of enhancing glucagon release in response to sympathetic activation. Arginine-induced but not NA-induced glucagon release from Sst-/- islets was significantly increased compared to controls. In combination, NA enhanced arginine-induced release from both groups of mouse islets but to a greater extent in control islets, leading to similar overall levels of glucagon release. The responsiveness of Sst-/- islets to NA was thus blunted under stimulatory but not sub-stimulatory conditions of SST release. CONCLUSIONS: Our data suggest that sympathetic activation of glucagon release may be partly mediated by an indirect effect on SST secretion, where the tonic inhibition by δ-cell SST on α-cells is removed, facilitating precise and substantial changes in glucagon release in response to NA.
Authors: M J Low; V Otero-Corchon; A F Parlow; J L Ramirez; U Kumar; Y C Patel; M Rubinstein Journal: J Clin Invest Date: 2001-06 Impact factor: 14.808
Authors: Yang Z De Marinis; Albert Salehi; Caroline E Ward; Quan Zhang; Fernando Abdulkader; Martin Bengtsson; Orit Braha; Matthias Braun; Reshma Ramracheya; Stefan Amisten; Abdella M Habib; Yusuke Moritoh; Enming Zhang; Frank Reimann; Anders Rosengren; Tadao Shibasaki; Fiona Gribble; Erik Renström; Susumu Seino; Lena Eliasson; Patrik Rorsman Journal: Cell Metab Date: 2010-06-09 Impact factor: 27.287
Authors: Jose Córdoba-Chacón; Manuel D Gahete; Ana I Pozo-Salas; Justo P Castaño; Rhonda D Kineman; Raul M Luque Journal: Endocrinology Date: 2013-05-21 Impact factor: 4.736
Authors: Alexander Hamilton; Quan Zhang; Albert Salehi; Mara Willems; Jakob G Knudsen; Anna K Ringgaard; Caroline E Chapman; Alejandro Gonzalez-Alvarez; Nicoletta C Surdo; Manuela Zaccolo; Davide Basco; Paul R V Johnson; Reshma Ramracheya; Guy A Rutter; Antony Galione; Patrik Rorsman; Andrei I Tarasov Journal: Diabetes Date: 2018-03-21 Impact factor: 9.461
Authors: Joely A Kellard; Nils J G Rorsman; Thomas G Hill; Sarah L Armour; Martijn van de Bunt; Patrik Rorsman; Jakob G Knudsen; Linford J B Briant Journal: Mol Metab Date: 2020-05-21 Impact factor: 7.422
Authors: Stefan Jacob; Concha F García-Prieto; Rafael Arrojo E Drigo; Xiaofeng Zheng; Masahiro Fukuda; Hoa Tran Thi Nhu; Olga Stelmashenko; Flavia Letícia Martins Peçanha; Rayner Rodriguez-Diaz; Eric Bushong; Thomas Deerinck; Sebastien Phan; Yusuf Ali; Ingo Leibiger; Minni Chua; Thomas Boudier; Sang-Ho Song; Martin Graf; George J Augustine; Mark H Ellisman; Per-Olof Berggren Journal: Nat Commun Date: 2019-08-16 Impact factor: 14.919
Authors: Patricio Atanes; Inmaculada Ruz-Maldonado; Ross Hawkes; Bo Liu; Min Zhao; Guo Cai Huang; Israa Mohammed Al-Amily; Albert Salehi; Stefan Amisten; Shanta J Persaud Journal: Cell Mol Life Sci Date: 2018-02-17 Impact factor: 9.261