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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.

Author:
  • 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
Publishing year: 2015
Language: English
Pages: 113-120
Publication/Series: Peptides
Volume: 71
Document type: Journal article
Publisher: Elsevier

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Celiac Unit
  • Diabetes and Endocrinology
  • Epigenetics and Diabetes
  • Molecular Metabolism
  • Islet patophysiology
  • Neuroendocrine Cell Biology
  • ISSN: 1873-5169
Peter Spegel
E-mail: peter.spegel [at] chem.lu.se

Researcher

Centre for Analysis and Synthesis

1

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00