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

Hedvig Bennet; Alexander Balhuizen; Anya Medina Benavente; Marloes Dekker Nitert; Emilia Ottosson Laakso; S Essén; Peter Spégel; Petter Storm; Ulrika Krus; Nils Wierup; Malin Fex

doi:10.1016/j.peptides.2015.07.008

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

Hedvig Bennet, Alexander Balhuizen, Anya Medina Benavente, Marloes Dekker Nitert, Emilia Ottosson Laakso, S Essén, Peter Spégel, Petter Storm, Ulrika Krus, Nils Wierup, Malin Fex

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	113-120
Journal	Peptides
Volume	71
DOIs	https://doi.org/10.1016/j.peptides.2015.07.008
Publication status	Published - 2015

Bibliographical note

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)

Subject classification (UKÄ)

Endocrinology and Diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.peptides.2015.07.008

http://www.ncbi.nlm.nih.gov/pubmed/26206285?dopt=Abstract

1 Doctoral Thesis (compilation)

Novel insights into the role of serotonin in control of β-cell fuction
Bennet, H., 2016, Unit of Diabetes and Celiac Disease. 78 p.
Research output: Thesis › Doctoral Thesis (compilation)

Cite this

Bennet, H., Balhuizen, A., Medina Benavente, A., Dekker Nitert, M., Ottosson Laakso, E., Essén, S., Spégel, P., Storm, P., Krus, U., Wierup, N., & 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. https://doi.org/10.1016/j.peptides.2015.07.008

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

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 = "Hedvig Bennet and Alexander Balhuizen and {Medina Benavente}, Anya and {Dekker Nitert}, Marloes and {Ottosson Laakso}, Emilia and S Ess{\'e}n and Peter Sp{\'e}gel and Petter Storm and Ulrika Krus and Nils Wierup and Malin Fex",

note = "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)",

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Bennet, H, Balhuizen, A, Medina Benavente, A, Dekker Nitert, M, Ottosson Laakso, E, Essén, S, Spégel, P , Storm, P, Krus, U, Wierup, N & 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, vol. 71, pp. 113-120. https://doi.org/10.1016/j.peptides.2015.07.008

TY - JOUR

T1 - Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.

AU - Bennet, Hedvig

AU - Balhuizen, Alexander

AU - Medina Benavente, Anya

AU - Dekker Nitert, Marloes

AU - Ottosson Laakso, Emilia

AU - Essén, S

AU - Spégel, Peter

AU - Storm, Petter

AU - Krus, Ulrika

AU - Wierup, Nils

AU - Fex, Malin

N1 - 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)

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.peptides.2015.07.008

DO - 10.1016/j.peptides.2015.07.008

M3 - Article

C2 - 26206285

SN - 1873-5169

VL - 71

SP - 113

EP - 120

JO - Peptides

JF - Peptides

ER -

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

Abstract

Bibliographical note

Subject classification (UKÄ)

UN SDGs

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Research output

Novel insights into the role of serotonin in control of β-cell fuction

Cite this