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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 71; pp. 113 - 120
• Main Authors: Bennet, H., Balhuizen, A., Medina, A., Dekker Nitert, M., Ottosson Laakso, E., Essén, S., Spégel, P., Storm, P., Krus, U., Wierup, N., Fex, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015
• Subjects: Clinical Medicine; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; G-protein coupled receptors; Gene Expression Regulation; Glucagon - metabolism; Human islets; Humans; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Receptor, Serotonin, 5-HT1D - biosynthesis; Receptor, Serotonin, 5-HT2A - biosynthesis; Serotonin; Signal Transduction; Type 2 diabetes; Type 2 diabetes; Human islets; Serotonin; G-protein coupled receptors
• ISSN: 0196-9781; 1873-5169; 1873-5169
• DOI: 10.1016/j.peptides.2015.07.008

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.