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Titel: Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels
VerfasserIn: Becker, Alexander
Mannebach, Stefanie
Mathar, Ilka
Weissgerber, Petra
Freichel, Marc
Loodin, Asia Perveen
Fecher-Trost, Claudia
Belkacemi, Anouar
Beck, Andreas
Philipp, Stephan Ernst
Sprache: Englisch
Titel: Cellular Physiology and Biochemistry
Bandnummer: 54
Startseite: 1115
Endseite: 1131
Verlag/Plattform: Cell Physiol Biochem Press GmbH & Co KG
Erscheinungsjahr: 2020
Freie Schlagwörter: Transient receptor potential M3 channels (TRPM3)
Calcium
Glucose-stimulated insulin secretion
CRISPR/Cas
INS-1
Trpm3 knockout
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background/Aims: The release of insulin in response to increased levels of glucose in the blood strongly depends on Ca2+ influx into pancreatic beta cells by the opening of voltage-gated Ca2+ channels. Transient Receptor Potential Melastatin 3 proteins build Ca2+ permeable, non-selective cation channels serving as pain sensors of noxious heat in the peripheral nervous system. TRPM3 channels are also strongly expressed in pancreatic beta cells that respond to the TRPM3 agonist pregnenolone sulfate with Ca2+ influx and increased insulin release. Therefore, we hypothesized that in beta cells TRPM3 channels may contribute to pregnenolone sulfate- as well as to glucose-induced insulin release. Methods: We used INS-1 cells as a beta cell model in which we analysed the occurrence of TRPM3 isoformes by immunoprecipitation and western blotting and by cloning of RT-PCR amplified cDNA fragments. We applied pharmacological as well as CRISPR/Cas9-based strategies to analyse the interplay of TRPM3 and voltage-gated Ca2+ channels in imaging experiments (FMP, Fura-2) and electrophysiological recordings. In immunoassays, we examined the contribution of TRPM3 channels to pregnenolone sulfate- and glucose-induced insulin release. To confirm our findings, we generated beta cell-specific Trpm3-deficient mice and compared their glucose clearance with the wild type in glucose tolerance tests. Results: TRPM3 channels triggered the activity of voltage-gated Ca2+ channels and both channels together contributed to insulin release after TRPM3 activation. Trpm3-deficient INS-1 cells lacked pregnenolone sulfate-induced Ca2+ signals just like the pregnenolone sulfate-induced insulin release. Both, glucose-induced Ca2+ signals and the glucose-induced insulin release were strongly reduced. Accordingly, Trpm3-deficient mice displayed an impaired decrease of the blood sugar concentration after intraperitoneal or oral administration of glucose. Conclusion: The present study suggests an important role for TRPM3 channels in the control of glucose-dependent insulin release.
DOI der Erstveröffentlichung: 10.33594/000000304
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-334772
hdl:20.500.11880/30775
http://dx.doi.org/10.22028/D291-33477
ISSN: 1421-9778
Datum des Eintrags: 1-Mär-2021
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professur: M - Prof. Dr. Veit Flockerzi
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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