Diabetologia (2017) 60:1731–1739 DOI 10.1007/s00125-017-4315-2 ARTICLE The role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice 1,2 1,2 Anne Ørgaard & Jens J. Holst Received: 7 March 2017 /Accepted: 10 April 2017 /Published online: 27 May 2017 The Author(s) 2017. This article is an open access publication Abstract +118.8%, respectively). Specific blockade of somatostatin re- Aims/hypothesis Glucagon-like peptide-1 (GLP-1) receptor ceptor 2 increased glucagon secretion (+118.8% at 1.5 mmol/l agonists are currently used for the treatment of type 2 diabetes. glucose and +162.9% at 6.0 mmol/l glucose) and completely Their main mechanism of action is enhancement of glucose- eliminated the inhibitory effect of GLP-1. induced insulin secretion (from increased beta cell glucose Conclusions/interpretation We have shown here that the sensitivity) and inhibition of glucagon secretion. The latter glucagon-lowering effect of GLP-1 is entirely mediated has been demonstrated to account for about half of their blood through the paracrine actions of somatostatin in the perfused glucose-lowering activity. Whereas the effect of GLP-1 on mouse pancreas. However, in this model, the inhibitory effect insulin secretion is clearly dependent on ambient glucose con- of GLP-1 was preserved at hypoglycaemic levels, leaving centrations and has been described in detail, the mechanism
Diabetologia – Springer Journals
Published: May 27, 2017
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