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Naslov:Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylation
Avtorji:ID Paulmann, Nils (Avtor)
ID Grohmann, Maik (Avtor)
ID Voigt, Jörg-Peter (Avtor)
ID Bert, Bettina (Avtor)
ID Vowinckel, Jakob (Avtor)
ID Bader, Michael (Avtor)
ID Skelin, Maša (Avtor)
ID Jevšek, Marko (Avtor)
ID Fink, Heidrun (Avtor)
ID Rupnik, Marjan (Avtor)
ID Walther, Diego (Avtor)
Datoteke:.pdf PLoS_Biology_2009_Paulmann_et_al._Intracellular_Serotonin_Modulates_Insulin_Secretion_from_Pancreatic_β-Cells_by_Protein_Serotonylation.PDF (774,75 KB)
MD5: 94CEBC5DBC3F2093108FCABC615596B9
 
URL http://dx.plos.org/10.1371/journal.pbio.1000229
 
Jezik:Angleški jezik
Vrsta gradiva:Znanstveno delo
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
Opis:While serotonin (5-HT) co-localization with insulin in granules of pancreatic ß-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is stili unclear. We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion. We found that these mice are diabetic and have an impaired insulin secretion due to the lack of 5-HT in the pancreas. The pharmacological restoration of peripheral 5-HT levels rescued the impaired insulin secretion in vivo. These findings were further evidenced by patch clamp experiments with isolated Tph1-/- ß-cells, which clearly showed that the secretory defect is downstream of Ca2+ -signaling and can be rescued by direct intracellular application of 5-HT via the clamp pipette. In elucidating the underlying mechanism further, we demonstrate the covalent coupling of 5-HT by transglutaminases during insulin exocytosis to two key players in insulin secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively active in a receptor-independent signaling mechanism we have recently termed serotonylation. Concordantly, an inhibition of such activating serotonylation in ß-cells abates insulin secretion. We also observed inactivation of serotonylated Rab3a by enhanced proteasomal degradation, which is in line with the inactivation of other serotonylated GTPases. Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic ß-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.
Ključne besede:insulin secretion, serotonin, insulin, glucose, diabetes mellitus, guanosine triphosphatase, exocytosis, pancreas
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Leto izida:2009
Št. strani:str. 1-10
Številčenje:Letn. 7, št. 10
PID:20.500.12556/DKUM-66246 Novo okno
ISSN:1544-9173
UDK:612
COBISS.SI-ID:63941377 Novo okno
DOI:10.1371/journal.pbio.1000229 Novo okno
ISSN pri članku:1544-9173
NUK URN:URN:SI:UM:DK:6HWSMNH2
Datum objave v DKUM:16.06.2017
Število ogledov:2195
Število prenosov:202
Metapodatki:XML DC-XML DC-RDF
Področja:Ostalo
:
PAULMANN, Nils, GROHMANN, Maik, VOIGT, Jörg-Peter, BERT, Bettina, VOWINCKEL, Jakob, BADER, Michael, SKELIN, Maša, JEVŠEK, Marko, FINK, Heidrun, RUPNIK, Marjan in WALTHER, Diego, 2009, Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylation. PLoS Biology [na spletu]. 2009. Vol. 7, no. 10, p. 1–10. [Dostopano 17 april 2025]. DOI 10.1371/journal.pbio.1000229. Pridobljeno s: https://dk.um.si/IzpisGradiva.php?lang=slv&id=66246
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Gradivo je del revije

Naslov:PLoS Biology
Skrajšan naslov:PLoS Biol.
Založnik:Public Library of Science
ISSN:1544-9173
COBISS.SI-ID:512779289 Novo okno

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:16.06.2017

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:izločanje inzulina, serotonin, inzulin, glukoza, sladkorna bolezen, diabetes mellitus, gvanozin-trifosfataza, eksocitoza, pankreas, trebušna slinavka


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