Advanced

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

Bennet, Hedvig LU ; Balhuizen, Alexander LU ; Medina Benavente, Anya LU ; Dekker Nitert, Marloes LU ; Ottosson Laakso, Emilia LU ; Essén, S; Spégel, Peter LU ; Storm, Petter LU ; Krus, Ulrika LU and Wierup, Nils LU , et al. (2015) In Peptides 71. p.113-120
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)... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Peptides
volume
71
pages
113 - 120
publisher
Elsevier
external identifiers
  • pmid:26206285
  • wos:000361837800015
  • scopus:84937847957
ISSN
1873-5169
DOI
10.1016/j.peptides.2015.07.008
language
English
LU publication?
yes
id
6b763ae8-8bec-4a70-a8b8-7d65bebc8f7a (old id 7713921)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26206285?dopt=Abstract
date added to LUP
2015-08-10 21:24:50
date last changed
2017-10-22 03:06:42
@article{6b763ae8-8bec-4a70-a8b8-7d65bebc8f7a,
  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.},
  author       = {Bennet, Hedvig and Balhuizen, Alexander and Medina Benavente, Anya and Dekker Nitert, Marloes and Ottosson Laakso, Emilia and Essén, S and Spégel, Peter and Storm, Petter and Krus, Ulrika and Wierup, Nils and Fex, Malin},
  issn         = {1873-5169},
  language     = {eng},
  pages        = {113--120},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.},
  url          = {http://dx.doi.org/10.1016/j.peptides.2015.07.008},
  volume       = {71},
  year         = {2015},
}