Serotonergic regulation of insulin secretion

Cataldo, Luis Rodrigo; Lyons, Claire L.; Bennet, Hedvig; Artner, Isabella; Fex, Malin

doi:10.1111/apha.13101

Cited by 49 publications

(47 citation statements)

References 91 publications

(160 reference statements)

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“…Townsend (University of Texas, Galveston, TX, USA). BON cells are functional with respect to secretion of serotonin [1,61], a monoamine that is released from a subset of pancreatic islet cells and β-cells along with insulin in a glucose-dependent manner [63]. The QGP-1 line was generated from a primary pancreatic carcinoma [2] and was purchased from the JCRB Cell Bank (Osaka, Japan).…”

Section: Cellsmentioning

confidence: 99%

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Luley

Biedermann

Künstner

et al. 2020

Cancers

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Experimental models of neuroendocrine tumor disease are scarce, with only a few existing neuroendocrine tumor cell lines of pancreatic origin (panNET). Their molecular characterization has so far focused on the neuroendocrine phenotype and cancer-related mutations, while a transcription-based assessment of their developmental origin and malignant potential is lacking. In this study, we performed immunoblotting and qPCR analysis of neuroendocrine, epithelial, developmental endocrine-related genes as well as next-generation sequencing (NGS) analysis of microRNAs (miRs) on three panNET cell lines, BON-1, QGP-1, and NT-3. All three lines displayed a neuroendocrine and epithelial phenotype; however, while insulinoma-derived NT-3 cells preferentially expressed markers of mature functional pancreatic β-cells (i.e., INS, MAFA), both BON-1 and QGP-1 displayed high expression of genes associated with immature or non-functional β/δ-cells genes (i.e., NEUROG3), or pancreatic endocrine progenitors (i.e., FOXA2). NGS-based identification of miRs in BON-1 and QGP-1 cells revealed the presence of all six members of the miR-17-92 cluster, which have been implicated in β-cell function and differentiation, but also have roles in cancer being both oncogenic or tumor suppressive. Notably, both BON-1 and QGP-1 cells expressed several miRs known to be negatively associated with epithelial-mesenchymal transition, invasion or metastasis. Moreover, both cell lines failed to exhibit migratory activity in vitro.Cancers 2020, 12, 691 2 of 18 Taken together, NT-3 cells resemble mature functional β-cells, while both BON-1 and QGP-1 are more similar to immature/non-functional pancreatic β/δ-cells or pancreatic endocrine progenitors. Based on the recent identification of three transcriptional subtypes in panNETs, NT-3 cells resemble the "islet/insulinoma tumors" (IT) subtype, while BON-1 and QGP-1 cells were tentatively classified as "metastasis-like/primary" (MLP). Our results provide a comprehensive characterization of three panNET cell lines and demonstrate their relevance as neuroendocrine tumor models.

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Section: Cellsmentioning

confidence: 99%

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Luley

Biedermann

Künstner

et al. 2020

Cancers

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“…HTR2B is abundantly expressed in human and rodent β-cells, where it initiates the phospholipase C beta (PLCβ)-inositol triphosphate (IP 3 )/diacylglycerol (DAG)-Ca 2+ cascade. The HTR2B agonist α-methyl serotonin maleate was shown to enhance glucose-stimulated insulin secretion in human and mouse islets by modulating Ca 2+ flux and increasing the mitochondrial oxygen consumption rate (Bennet et al 2016, Cataldo Bascunan et al 2019. HTR2B knock-down in INS-1 cells resulted in impaired insulin secretion (Bennet et al 2016), whereas disruption of HTR2B in adult β-cells using MIP-CreER did not affect glucose tolerance (Kim et al 2015).…”

Section: Metabolic Roles Of 5-ht In Pancreatic β-Cellsmentioning

confidence: 99%

Serotonergic regulation of energy metabolism in peripheral tissues

Choi

Moon

Kim

2020

Journal of Endocrinology

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Serotonin is a biogenic amine synthesized from the essential amino acid tryptophan. Because serotonin cannot cross the blood-brain barrier, it functions differently in neuronal and non-neuronal tissues. In the CNS, serotonin regulates mood, behavior, appetite, and energy expenditure. Although most serotonin in the body is synthesized at the periphery, its biological roles have not been well elucidated. Older studies using chemical agonists and antagonists yielded conflicting results, because the complexity of serotonin receptors and the low selectivity of agonists and antagonists were not known. Several recent studies using specific knock-out of serotonin receptors have been performed to assess the role of peripheral serotonin in regulating energy metabolism. This review discusses (1) the tissue-specific roles of peripheral serotonin in regulating energy metabolism, (2) the mechanism by which dysfunctional peripheral serotonin signaling can progress to metabolic diseases, and (3) how peripheral serotonin signaling could be a therapeutic target for metabolic diseases.

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“…5HT signaling is transduced by a large and complex receptor family composed of fourteen subtypes [8]. Thus, locally produced or platelet-derived 5HT may theoretically act either as a hormone or as an autocrine/paracrine factor, whose diverse metabolic effects are mediated by the specific set of 5HT receptors expressed or activated in target cells [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Platelet Serotonin Levels Are Associated with Plasma Soluble Leptin Receptor Concentrations in Normoglycemic Women

Cataldo

Suazo

Olmos

et al. 2019

Journal of Diabetes Research

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Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (r=0.39, p=0.003, corrected p=0.018). Platelet 5HT levels were reduced in response to OGTT (779±237 vs.731±217 ng/109 platelets, p=0.005). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation.

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Serotonergic regulation of insulin secretion

Cited by 49 publications

References 91 publications

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Serotonergic regulation of energy metabolism in peripheral tissues

Platelet Serotonin Levels Are Associated with Plasma Soluble Leptin Receptor Concentrations in Normoglycemic Women

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