A role for islet somatostatin in mediating sympathetic regulation of glucagon secretion

• Published in: Islets 2010-11, Vol.2 (6), p.341-344
• Main Authors: Hauge-Evans, Astrid C., King, Aileen, Fairhall, Keith, Jones, Peter M.
• Format: Article
• Language: English
• Subjects: Animals; Arginine - metabolism; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Female; Glucagon - secretion; Glucagon-Secreting Cells - metabolism; Glucagon-Secreting Cells - secretion; Glucose - metabolism; Insulin-Secreting Cells - metabolism; Islets of Langerhans - innervation; Islets of Langerhans - metabolism; Islets of Langerhans - secretion; Landes; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Norepinephrine - metabolism; Organ Culture Techniques; Organogenesis; Paracrine Communication; Proteins; Short Report; Somatostatin - genetics; Somatostatin - physiology; Somatostatin - secretion; Sympathetic Nervous System - metabolism; Synaptic Transmission
• ISSN: 1938-2014; 1938-2022
• DOI: 10.4161/isl.2.6.13858

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.