Downloads and Tools

•  Article PDF
  458.73 KB PDF document

This is an open access article.
Print this page Email this page

Recipient's Email:

---

Article Citation

RIS
MARC (XML)
FULL CITATION (TXT)

---

Share on Facebook

Authors: Astrid C. Hauge-Evans, Aileen King, Keith Fairhall, and Peter M. Jones

Astrid C. Hauge-Evans

Corresponding author: astrid.hauge_evans@kcl.ac.uk
Diabetes Research Group; King’s College London; Molecular Neuroendocrinology, Neurophysiology and Physical Biochemistry; MRC National Institute for Medical Research; London, UK

Aileen King

Diabetes Research Group; King’s College London; Molecular Neuroendocrinology, Neurophysiology and Physical Biochemistry; MRC National Institute for Medical Research; London, UK

Keith Fairhall

Diabetes Research Group; King’s College London; Molecular Neuroendocrinology, Neurophysiology and Physical Biochemistry; MRC National Institute for Medical Research; London, UK

Peter M. Jones

Diabetes Research Group; King’s College London; Molecular Neuroendocrinology, Neurophysiology and Physical Biochemistry; MRC National Institute for Medical Research; London, UK

Abstract:
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.

Received: September 3, 2010; Accepted: October 4, 2010

Preview: