Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans

Bennet, Hedvig, Mollet, Inês G., Balhuizen, Alexander, Medina, Anya, Nagorny, Cecilia, Bagge, Annika, Fadista, Joao, Ottosson-Laakso, Emilia, Vikman, Petter, Dekker-Nitert, Marloes, Eliasson, Lena, Wierup, Nils, Artner, Isabella and Fex, Malin (2016) Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans. Diabetologia, 59 4: 744-754. doi:10.1007/s00125-015-3847-6


Author Bennet, Hedvig
Mollet, Inês G.
Balhuizen, Alexander
Medina, Anya
Nagorny, Cecilia
Bagge, Annika
Fadista, Joao
Ottosson-Laakso, Emilia
Vikman, Petter
Dekker-Nitert, Marloes
Eliasson, Lena
Wierup, Nils
Artner, Isabella
Fex, Malin
Title Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans
Journal name Diabetologia   Check publisher's open access policy
ISSN 1432-0428
0012-186X
Publication date 2016-04-01
Sub-type Article (original research)
DOI 10.1007/s00125-015-3847-6
Open Access Status Not Open Access
Volume 59
Issue 4
Start page 744
End page 754
Total pages 11
Place of publication Heidelberg, Germany
Publisher Springer Verlag
Language eng
Formatted abstract
Aims/hypothesis
The Gq-coupled 5-hydroxytryptamine 2B (5-HT2B) receptor is known to regulate the proliferation of islet beta cells during pregnancy. However, the role of serotonin in the control of insulin release is still controversial. The aim of the present study was to explore the role of the 5-HT2B receptor in the regulation of insulin secretion in mouse and human islets, as well as in clonal INS-1(832/13) cells.

Methods
Expression of HTR2B mRNA and 5-HT2B protein was examined with quantitative real-time PCR, RNA sequencing and immunohistochemistry. α-Methyl serotonin maleate salt (AMS), a serotonin receptor agonist, was employed for robust 5-HT2B receptor activation. Htr2b was silenced with small interfering RNA in INS-1(832/13) cells. Insulin secretion, Ca2+ response and oxygen consumption rate were determined.

Results
Immunohistochemistry revealed that 5-HT2B is expressed in human and mouse islet beta cells. Activation of 5-HT2B receptors by AMS enhanced glucose-stimulated insulin secretion (GSIS) in human and mouse islets as well as in INS-1(832/13) cells. Silencing Htr2b in INS-1(832/13) cells led to a 30% reduction in GSIS. 5-HT2B receptor activation produced robust, regular and sustained Ca2+ oscillations in mouse islets with an increase in both peak distance (period) and time in the active phase as compared with control. Enhanced insulin secretion and Ca2+ changes induced by AMS coincided with an increase in oxygen consumption in INS-1(832/13) cells.

Conclusions/interpretation
Activation of 5-HT2B receptors stimulates GSIS in beta cells by triggering downstream changes in cellular Ca2+ flux that enhance mitochondrial metabolism. Our findings suggest that serotonin and the 5-HT2B receptor stimulate insulin release.
Keyword Beta cell
Ca2+ oscillations
G protein-coupled receptor
Human islets of Langerhans
Insulin secretion
Mitochondrial respiration
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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