Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide,inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas |
| |
Authors: | J de Heer C Rasmussen D H Coy J J Holst |
| |
Institution: | (1) Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark;(2) Peptide Research Laboratories, Tulane University School of Medicine, New Orleans, LA, USA |
| |
Abstract: | Aims/hypothesis The glucose-lowering effect of glucagon-like peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but
also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide
(GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion,
is involved in this divergent behaviour.
Methods At 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l
glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and
of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas.
Results In control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0 ± 6.3% (p < 0.004; n = 5; SSTR2 series; each vs pre-infusion level) and to 48.0 ± 2.6% (p < 0.001; n = 6; somatostatin antibody series) respectively. During somatostatin antibody administration, GLP-1 still inhibited glucagon
secretion significantly, but the effect was less pronounced than in control experiments (p < 0.018). Co-infusion of the SSTR2 antagonist completely abolished the GLP-1-induced suppression of glucagon secretion. In
contrast, neither the GIP-induced stimulation of glucagon release nor its inhibition by 20 mmol/l glucose was altered by somatostatin
antibody or SSTR2 antagonist administration.
Conclusions/interpretation We conclude that GLP-1 is capable of inhibiting glucagon secretion even in the absence of secretory products from the beta
cell. It is highly likely that this is mediated via somatostatin interacting with SSTR2 on rat alpha cells. In contrast, GIP
and glucose seem to influence the alpha cell independently of somatostatin secretion. |
| |
Keywords: | GIP GLP-1 Glucagon Gut hormones Insulin Paracrine Perfused rat pancreas Somatostatin |
本文献已被 PubMed SpringerLink 等数据库收录! |
|