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

被引：82

作者：

Bennet, H. ^{[1
]}

Balhuizen, A. ^{[1
]}

Medina, A. ^{[1
]}

Nitert, M. Dekker ^{[1
,2
]}

Laakso, E. Ottosson ^{[1
]}

Essen, S. ^{[3
]}

Spegel, P. ^{[1
]}

Storm, P. ^{[1
]}

Krus, U. ^{[1
]}

Wierup, N. ^{[1
]}

Fex, M. ^{[1
]}

机构：

[1] Lund Univ, Ctr Diabet, Scania Univ Hosp, Dept Clin Sci, SE-20502 Malmo, Sweden

[2] Univ Queensland, UQ Ctr Clin Res, Royal Brisbane Clin Sch, Herston, Qld 4029, Australia

[3] Lund Univ, Ctr Anal & Synth, Dept Chem, SE-22241 Lund, Sweden

来源：

PEPTIDES | 2015年 / 71卷

基金：

瑞典研究理事会;

关键词：

Human islets; Serotonin; G-protein coupled receptors; Type; 2; diabetes; PANCREATIC BETA-CELLS; SELECTIVE SEROTONIN; GLUCOSE; DOPAMINE; ISLETS; 5-HYDROXYTRYPTAMINE; INHIBITION; ANTAGONIST; ACTIVATION; ALPHA;

D O I：

10.1016/j.peptides.2015.07.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：113 / 120

页数：8

共 48 条

[1]

Adeghate Ernest, 1999, Neuro Endocrinol Lett, V20, P315

[2] Autonomic regulation of islet hormone secretion -: Implications for health and disease [J].

Ahrén, B .

DIABETOLOGIA, 2000, 43 (04) :393-410

[3] An atlas and functional analysis of G-protein coupled receptors in human islets of Langerhans [J].

Amisten, Stefan ;

Salehi, Albert ;

Rorsman, Patrik ;

Jones, Peter M. ;

Persaud, Shanta J. .

PHARMACOLOGY & THERAPEUTICS, 2013, 139 (03) :359-391

[4] HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13 [J].

Asad, Samina ;

Nikamo, Pernilla ;

Gyllenberg, Alexandra ;

Bennet, Hedvig ;

Hansson, Ola ;

Wierup, Nils ;

Carlsson, Annelie ;

Forsander, Gun ;

Ivarsson, Sten-Anders ;

Larsson, Helena ;

Lernmark, Ake ;

Lindblad, Bengt ;

Ludvigsson, Johnny ;

Marcus, Claude ;

Ronningen, Kjersti S. ;

Nerup, Jan ;

Pociot, Flemming ;

Luthman, Holger ;

Fex, Malin ;

Kockum, Ingrid .

PLOS ONE, 2012, 7 (05)

[5] THE PHARMACOLOGY AND DISTRIBUTION OF HUMAN 5-HYDROXYTRYPTAMINE(2B) (5-HT2B) RECEPTOR GENE-PRODUCTS - COMPARISON WITH 5-HT2A AND 5-HT2C RECEPTORS [J].

BONHAUS, DW ;

BACH, C ;

DESOUZA, A ;

SALAZAR, FHR ;

MATSUOKA, BD ;

ZUPPAN, P ;

CHAN, HW ;

EGLEN, RM .

BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (04) :622-628

[6] Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2 [J].

Bos, Remi ;

Sadlaoud, Karina ;

Boulenguez, Pascale ;

Buttigieg, Dorothee ;

Liabeuf, Sylvie ;

Brocard, Cecile ;

Haase, Georg ;

Bras, Helene ;

Vinay, Laurent .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (01) :348-353

[7]

BRAMSWIG NC, 2013, J CLIN INVEST, V0123

[8]

Cegrell L., 1968, Acta Physiologica Scandinavica Suppl, V314, P1

[9]

CHAOULOFF F, 1987, J PHARMACOL EXP THER, V243, P1159

[10] 5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans [J].

Coulie, B ;

Tack, J ;

Bouillon, R ;

Peeters, T ;

Janssens, J .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1998, 274 (02) :E317-E320

← 1 2 3 4 5 →