Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.
(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:
https://lup.lub.lu.se/record/7713921
- author
- organization
-
- Celiac Disease and Diabetes Unit (research group)
- Translational Muscle Research (research group)
- Diabetes - Epigenetics (research group)
- Department of Experimental Medical Science
- Diabetes - Molecular Metabolism (research group)
- Diabetes - Islet Patophysiology (research group)
- Neuroendocrine Cell Biology (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- publishing date
- 2015
- 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}}, }