Estrogen and Serotonin – old dogs, new tricks, Implications for pancreatic beta-cell function
type: CreativeWork
description: Islet hormone secretion is tightly regulated by metabolic status as well as local and circulating factors. These factors can activate different receptors on the pancreatic islet cells, for instance G-protein coupled receptors (GPCRs). When activated, these receptors are able to fine-tune islet hormone secretion and regulate overall β-cell function. Estrogen and serotonin are circulating factors that bind to GPCRs. First, we studied the activation of GPER-1 in pancreatic islets using two agonists G-1 and Estrogen (E2). Both G-1 and E2 displayed a similar response in mouse and human islets even in the presence of estrogen receptor blockers, ICI 182, 720 and EM652. G-1 and E2 potentiated insulin secretion and inhibited glucagon and somatostatin secretion. G-1 induced cAMP generation, suggesting positive coupling to adenylate cyclase and a subsequent rise in insulin release. Furthermore both agonists protected pancreatic islets from cytokine-induced apoptosis via activation of anti-apoptotic signals, CREB, ERK1/2 and AKT and reduced phosphorylation of the pro-apoptotic signals SAPK/JNK and p38. Second, we studied serotonin (5-HT) receptors in human islets and INS (832/13) cells. We detected 15 different 5-HT receptors and the 5-HT producing enzymes, TPH1 and TPH2 as well as DDC. Cellular localization for 5-HT1A, 5-HT1D and 5-HT2A were observed in both β- and α-cells; while 5-HT2B was only present in β-cells. Agonists targeting these four receptors were able to either inhibit or stimulate insulin secretion from human islets and INS (832/13) cells. In addition, 5-HT was quantified using GC/MS in INS (832/13) cells, rat islets and detected in human α and β-cells with immunohistochemistry. Third, we investigated the peripheral role of a 5-HT2 receptor agonist, α-methyl serotonin maleate salt (AMS) in insulin resistance and β cell function. Long-term treatment with AMS in a high fat diet fed mouse model resulted in increased insulin sensitivity in vivo in high fat fed AMS tr…
abstract: Islet hormone secretion is tightly regulated by metabolic status as well as local and circulating factors. These factors can activate different receptors on the pancreatic islet cells, for instance G-protein coupled receptors (GPCRs). When activated, these receptors are able to fine-tune islet hormone secretion and regulate overall β-cell function. Estrogen and serotonin are circulating factors that bind to GPCRs. First, we studied the activation of GPER-1 in pancreatic islets using two agonists G-1 and Estrogen (E2). Both G-1 and E2 displayed a similar response in mouse and human islets even in the presence of estrogen receptor blockers, ICI 182, 720 and EM652. G-1 and E2 potentiated insulin secretion and inhibited glucagon and somatostatin secretion. G-1 induced cAMP generation, suggesting positive coupling to adenylate cyclase and a subsequent rise in insulin release. Furthermore both agonists protected pancreatic islets from cytokine-induced apoptosis via activation of anti-apoptotic signals, CREB, ERK1/2 and AKT and reduced phosphorylation of the pro-apoptotic signals SAPK/JNK and p38. Second, we studied serotonin (5-HT) receptors in human islets and INS (832/13) cells. We detected 15 different 5-HT receptors and the 5-HT producing enzymes, TPH1 and TPH2 as well as DDC. Cellular localization for 5-HT1A, 5-HT1D and 5-HT2A were observed in both β- and α-cells; while 5-HT2B was only present in β-cells. Agonists targeting these four receptors were able to either inhibit or stimulate insulin secretion from human islets and INS (832/13) cells. In addition, 5-HT was quantified using GC/MS in INS (832/13) cells, rat islets and detected in human α and β-cells with immunohistochemistry. Third, we investigated the peripheral role of a 5-HT2 receptor agonist, α-methyl serotonin maleate salt (AMS) in insulin resistance and β cell function. Long-term treatment with AMS in a high fat diet fed mouse model resulted in increased insulin sensitivity in vivo in high fat fed AMS tr…
author: Balhuizen, Alexander
language: eng
keywords: Endocrinology and Diabetes, Diabetes, Estrogen, Serotonin, Pancreatic islets, Insulin resistance, Beta-cell function, GPCR
date published: 2013
date modified: 2026-07-24T02:59:49Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Diabetes and Celiac Unit