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doi:10.22028/D291-44088
Titel: | Regulation and function of AP-1 in insulinoma cells and pancreatic β-cells |
VerfasserIn: | Backes, Tobias M. Langfermann, Daniel S. Lesch, Andrea Rössler, Oliver G. Laschke, Matthias W. Vinson, Charles Thiel, Gerald |
Sprache: | Englisch |
Titel: | Biochemical Pharmacology |
Bandnummer: | 193 |
Verlag/Plattform: | Elsevier |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | AP-1 ATF2 Cav1.2 channel c-Jun Glucose tolerance Pancreatic β-cells |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Cav1.2 L-type voltage-gated Ca2+ channels play a central role in pancreatic β-cells by integrating extracellular signals with intracellular signaling events leading to insulin secretion and altered gene transcription. Here, we investigated the intracellular signaling pathway following stimulation of Cav1.2 Ca2+ channels and addressed the function of the transcription factor activator protein-1 (AP-1) in pancreatic β-cells of transgenic mice. Stimulation of Cav1.2 Ca2+ channels activates AP-1 in insulinoma cells. Pharmacological and genetic experiments identified c-Jun N-terminal protein kinase as a signal transducer connecting Cav1.2 Ca2+ channel activation with gene transcription. Moreover, the basic region-leucine zipper proteins ATF2 and c-Jun or c-Jun-related proteins were involved in stimulus-transcription coupling. We addressed the functions of AP-1 in pancreatic β-cells analyzing a newly generated transgenic mouse model. These transgenic mice expressed A-Fos, a mutant of c-Fos that attenuates DNA binding of c-Fos dimerization partners. In insulinoma cells, A-Fos completely blocked AP-1 activation following stimulation of Cav1.2 Ca2+ channels. The analysis of transgenic A-Fos-expressing mice revealed that the animals displayed impaired glucose tolerance. Thus, we show here for the first time that AP-1 controls an important function of pancreatic β-cells in vivo, the regulation of glucose homeostasis. |
DOI der Erstveröffentlichung: | 10.1016/j.bcp.2021.114748 |
URL der Erstveröffentlichung: | https://doi.org/10.1016/j.bcp.2021.114748 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-440881 hdl:20.500.11880/39440 http://dx.doi.org/10.22028/D291-44088 |
ISSN: | 1873-2968 |
Datum des Eintrags: | 22-Jan-2025 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Chirurgie M - Medizinische Biochemie und Molekularbiologie |
Professur: | M - Prof. Dr. Michael D. Menger M - Prof. Dr. Gerald Thiel |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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