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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 orcid ; 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)
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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
  • pmid:26206285
ISSN
1873-5169
DOI
10.1016/j.peptides.2015.07.008
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Islet patophysiology (013212132), Diabetes and Celiac Unit (013241540), Diabetes and Endocrinology (013241530), Molecular Metabolism (013244000), Molecular Metabolism (013212001), Faculty of Medicine (000022000), Epigenetics and Diabetes (013241505), Neuroendocrine Cell Biology (013241501)
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
2016-04-01 10:04:51
date last changed
2024-04-21 02:43:20
@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}},
  doi          = {{10.1016/j.peptides.2015.07.008}},
  volume       = {{71}},
  year         = {{2015}},
}