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

Peptides. 2015 Sep;71:113-20. doi: 10.1016/j.peptides.2015.07.008. Epub 2015 Jul 20.

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.

Keywords: G-protein coupled receptors; Human islets; Serotonin; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Gene Expression Regulation
  • Glucagon / metabolism*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Receptor, Serotonin, 5-HT1D / biosynthesis*
  • Receptor, Serotonin, 5-HT2A / biosynthesis*
  • Signal Transduction

Substances

  • Insulin
  • Receptor, Serotonin, 5-HT1D
  • Receptor, Serotonin, 5-HT2A
  • Glucagon