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

Publication date: Available online 20 July 2015 Source:Peptides Author(s): H. Bennet, A. Balhuizen, A. Medina, M. Dekker Nitert, E. Ottosson Laakso, S. Essén, P. Spégel, P. Storm, U. Krus, N. Wierup, M. Fex 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 the 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 and while 5-HT inhibited both insulin and glucagon secretion in non-diabetic islet donors, 5-HT significantly increased the release of insulin in response to glucose in islets isolated from T2D donors. Attempting to understand the consequences of altered 5-HT receptor expression in the diabetic islet, we investigated the specific function of receptors 5-HT1d and 5-HT2a in non-diabetic islets. We found that a 5-HT1d receptor agonist inhibited insulin release while a 5-H...
Source: Peptides - Category: Biochemistry Source Type: research