<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion"^^ . "Secretion of insulin in response to extracellular stimuli, such as elevated glucose levels and small\r\nmolecules that act on G-protein coupled receptors (GPCRs), is the hallmark of β-cell physiology.\r\nSufficiently high blood insulin levels are ensured by the coupling of the secretory activity within\r\npancreatic islets. Intercellular and inter-islet coordination are partly mediated by small diffusible\r\nligands of GPCRs within the extracellular space of pancreatic islets. Therefore, insulin release is\r\nconsidered a synchronized multi-cellular process. We show herein that β-cell activity and insulin\r\nsecretion essentially rely on the presence of extracellular endogenous (autocrine) signaling factors,\r\nexemplified by two classes of small cellular metabolites.\r\nTrace amines (TAs) are small aromatic metabolites that were identified as low-abundant ligands of\r\nthe trace amine-associated receptor 1 (TAAR1) in the central nervous system (CNS). In the\r\npresented work, we identify TAs as essential autocrine signaling factors that maintain and regulate\r\noscillations of the intracellular Ca2+ concentration ([Ca2+]i oscillations) along with insulin secretion\r\nfrom β-cells via TAAR1. We found that the modulation of endogenous TA levels by the selective\r\ninhibition of TA biosynthetic pathways directly translated into changes of [Ca2+]i oscillations and\r\ninsulin secretion. Application of aromatic amine-withdrawing β-cyclodextrin temporarily reduced\r\n[Ca2+]i oscillations. This demonstrates the essential role of TAs for β-cell activity as well as their\r\nhigh metabolic turnover rates. Notably, herein applied inhibitors and synthetic TAAR1\r\n(ant-)agonists are partly approved for the therapeutic modulation of biogenic amine levels within\r\nthe CNS, and hence for the treatment of common neurological disorders. According to our findings,\r\nthese drugs even affect β-cell activity and insulin secretion through pancreatic TAAR1.\r\nWith the discovery of the free fatty acid (FA) receptor GPR40 in β-cells, FAs have come into focus\r\nas exogenous insulin secretagogues. However, the role of FAs as endogenous (local) signaling\r\nfactors of β-cells has not been considered so far. We show herein that lowering endogenous FAlevels\r\nin the presence of FA-free bovine serum albumin (FAF-BSA) immediately reduced [Ca2+]i\r\noscillations and insulin secretion. [Ca2+]i oscillations resumed upon exchange of FAF-BSA by\r\nbuffer or upon restoration of extracellular FA pools. The latter was accomplished by the photolysis\r\nof caged FAs on plasma membranes, by the addition of a recombinant lipase or of FA-loaded BSA.\r\nOur approach to subordinate β-cell activity and insulin secretion to the presence of autocrine\r\nsignaling factors of the yet underestimated receptors TAAR1 and GPR40 in the pancreas\r\ncontributes to a more detailed and complete understanding of the fundamental regulation of β-cell\r\nactivity and insulin secretion."^^ . "2019" . . . . . . . "Sebastian"^^ . "Hauke"^^ . "Sebastian Hauke"^^ . . . . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (PDF)"^^ . . . "Dissertation S_Hauke.pdf"^^ . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Investigations of Trace Amines and Fatty Acids as Essential\r\nEndogenous Signaling Factors for β-Cell Activity\r\nand Insulin Secretion (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #26060 \n\nInvestigations of Trace Amines and Fatty Acids as Essential \nEndogenous Signaling Factors for β-Cell Activity \nand Insulin Secretion\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "540 Chemie"@de . "540 Chemistry and allied sciences"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .