Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes

Bennet, H., Balhuizen, A., Medina, A., Dekker Nitert, M., Ottosson Laakso, E., Essen, S., Spegel, P., Storm, P., Krus, U., Wierup, N. and Fex, M. (2015) Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes. Peptides, 71 113-120. doi:10.1016/j.peptides.2015.07.008


Author Bennet, H.
Balhuizen, A.
Medina, A.
Dekker Nitert, M.
Ottosson Laakso, E.
Essen, S.
Spegel, P.
Storm, P.
Krus, U.
Wierup, N.
Fex, M.
Title Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes
Journal name Peptides   Check publisher's open access policy
ISSN 0196-9781
1873-5169
Publication date 2015-07-27
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.peptides.2015.07.008
Open Access Status Not Open Access
Volume 71
Start page 113
End page 120
Total pages 8
Place of publication Philadelphia, PA United States
Publisher Elsevier
Collection year 2016
Language eng
Formatted abstract
Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies demonstrate a role for this amine in human islet function, nor is it known if 5-HT signaling is involved in the development of beta cell dysfunction in type 2 diabetes (T2D). To clarify this, we performed a complete transcriptional mapping of 5-HT receptors and processing enzymes in human islets and investigated differential expression of these genes in non-diabetic and T2D human islet donors. We show the expression of fourteen 5-HT receptors as well as processing enzymes involved in the biosynthesis of 5-HT at the mRNA level in human islets. Two 5-HT receptors (HTR1D and HTR2A) were over-expressed in T2D islet donors. Both receptors (5-HT1d and 5-HT2a) were localized to human alpha, beta and delta cells. 5-HT inhibited both insulin and glucagon secretion in non-diabetic islet donors. In islets isolated from T2D donors the amine significantly increased release of insulin in response to glucose. Our results suggest that 5-HT signaling participates in regulation of overall islet hormone secretion in non- diabetic individuals and over-expression of HTR1D and HTR2A may either contribute to islet dysfunction in T2D or arise as a consequence of an already dysfunctional islet.
Keyword G-protein coupled receptors
Human islets
Serotonin
Type 2 diabetes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
 
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