Title |
Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans
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Published in |
Diabetologia, January 2016
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DOI | 10.1007/s00125-015-3847-6 |
Pubmed ID | |
Authors |
Hedvig Bennet, Inês G. Mollet, Alexander Balhuizen, Anya Medina, Cecilia Nagorny, Annika Bagge, Joao Fadista, Emilia Ottosson-Laakso, Petter Vikman, Marloes Dekker-Nitert, Lena Eliasson, Nils Wierup, Isabella Artner, Malin Fex |
Abstract |
The Gq-coupled 5-hydroxytryptamine 2B (5-HT2B) receptor is known to regulate the proliferation of islet beta cells during pregnancy. However, the role of serotonin in the control of insulin release is still controversial. The aim of the present study was to explore the role of the 5-HT2B receptor in the regulation of insulin secretion in mouse and human islets, as well as in clonal INS-1(832/13) cells. Expression of HTR2B mRNA and 5-HT2B protein was examined with quantitative real-time PCR, RNA sequencing and immunohistochemistry. α-Methyl serotonin maleate salt (AMS), a serotonin receptor agonist, was employed for robust 5-HT2B receptor activation. Htr2b was silenced with small interfering RNA in INS-1(832/13) cells. Insulin secretion, Ca(2+) response and oxygen consumption rate were determined. Immunohistochemistry revealed that 5-HT2B is expressed in human and mouse islet beta cells. Activation of 5-HT2B receptors by AMS enhanced glucose-stimulated insulin secretion (GSIS) in human and mouse islets as well as in INS-1(832/13) cells. Silencing Htr2b in INS-1(832/13) cells led to a 30% reduction in GSIS. 5-HT2B receptor activation produced robust, regular and sustained Ca(2+) oscillations in mouse islets with an increase in both peak distance (period) and time in the active phase as compared with control. Enhanced insulin secretion and Ca(2+) changes induced by AMS coincided with an increase in oxygen consumption in INS-1(832/13) cells. Activation of 5-HT2B receptors stimulates GSIS in beta cells by triggering downstream changes in cellular Ca(2+) flux that enhance mitochondrial metabolism. Our findings suggest that serotonin and the 5-HT2B receptor stimulate insulin release. |
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Geographical breakdown
Country | Count | As % |
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Canada | 1 | 33% |
Finland | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
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United Kingdom | 1 | 2% |
Unknown | 64 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 12 | 18% |
Researcher | 9 | 14% |
Student > Bachelor | 7 | 11% |
Student > Master | 5 | 8% |
Other | 3 | 5% |
Other | 11 | 17% |
Unknown | 18 | 28% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 13 | 20% |
Biochemistry, Genetics and Molecular Biology | 11 | 17% |
Agricultural and Biological Sciences | 9 | 14% |
Chemistry | 3 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Other | 6 | 9% |
Unknown | 21 | 32% |