Paracrine regulation of somatostatin secretion by insulin and glucagon in mouse pancreatic islets.
Animals
Arginine
/ administration & dosage
Cell Communication
Diphtheria Toxin
/ pharmacology
Gene Knockdown Techniques
Glucagon
/ administration & dosage
Glucagon-Like Peptide-1 Receptor
/ drug effects
Glucagon-Secreting Cells
/ drug effects
Glucose
/ administration & dosage
Insulin
/ administration & dosage
Insulin Secretion
/ drug effects
Islets of Langerhans
/ drug effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Glucagon
/ deficiency
Receptors, Somatostatin
/ antagonists & inhibitors
Signal Transduction
/ physiology
Somatostatin
/ administration & dosage
Glucagon
Intra-islet communication
Perfused mouse pancreas
Somatostatin secretion
Journal
Diabetologia
ISSN: 1432-0428
Titre abrégé: Diabetologia
Pays: Germany
ID NLM: 0006777
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
07
05
2020
accepted:
26
07
2020
pubmed:
13
10
2020
medline:
7
1
2022
entrez:
12
10
2020
Statut:
ppublish
Résumé
The endocrine pancreas comprises the islets of Langerhans, primarily consisting of beta cells, alpha cells and delta cells responsible for secretion of insulin, glucagon and somatostatin, respectively. A certain level of intra-islet communication is thought to exist, where the individual hormones may reach the other islet cells and regulate their secretion. Glucagon has been demonstrated to importantly regulate insulin secretion, while somatostatin powerfully inhibits both insulin and glucagon secretion. In this study we investigated how secretion of somatostatin is regulated by paracrine signalling from glucagon and insulin. Somatostatin secretion was measured from perfused mouse pancreases isolated from wild-type as well as diphtheria toxin-induced alpha cell knockdown, and global glucagon receptor knockout (Gcgr A tonic inhibitory role of somatostatin was demonstrated with infusion of somatostatin receptor antagonists, which significantly increased glucagon secretion at low and high glucose, whereas insulin secretion was only increased at high glucose levels. Infusion of glucagon dose-dependently increased somatostatin secretion approximately twofold in control mice. Exogenous glucagon had no effect on somatostatin secretion in Gcgr Our findings demonstrate that somatostatin and glucagon secretion are linked in a reciprocal feedback cycle with somatostatin inhibiting glucagon secretion at low and high glucose levels, and glucagon stimulating somatostatin secretion via the glucagon and GLP-1 receptors. Graphical abstract.
Identifiants
pubmed: 33043402
doi: 10.1007/s00125-020-05288-0
pii: 10.1007/s00125-020-05288-0
doi:
Substances chimiques
Diphtheria Toxin
0
Glucagon-Like Peptide-1 Receptor
0
Insulin
0
Receptors, Glucagon
0
Receptors, Somatostatin
0
Somatostatin
51110-01-1
Glucagon
9007-92-5
Arginine
94ZLA3W45F
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
142-151Subventions
Organisme : European Foundation for the Study of Diabetes
ID : EFSD-Lilly Young Investigator Research Award 2019
Organisme : Novo Nordisk Foundation
ID : Center for Basic Metabolic Research
Organisme : Lundbeckfonden
ID : 2016-2394
Organisme : Det Frie Forskningsråd
ID : 6110-00660
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