Univerzitetna knjižnica Maribor (UKM)
Knjižnica je med tednom odprta od 8. do 14. ure, ob sredah do 17. ure ter ob sobotah od 9. do 13. ure. Čitalnica ČUK je odprta od ponedeljka do sobote od 12. do 24. ure, ob nedeljah je zaprta. Informacije: 02 25 07 431, ukm@um.si
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Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylationPaulmann, Nils ...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.Vir: PLoS biology [Elektronski vir]. - ISSN 1545-7885 (Vol. 7, iss. 10, oct. 2009, 10 str.)Vrsta gradiva - članek, sestavni delLeto - 2009Jezik - angleškiCOBISS.SI-ID - 63941377
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Paulmann, Nils | |
Grohmann, Maik | |
Voigt, Jörg-Peter | |
Bert, Bettina | |
Vowinckel, Jakob | |
Bader, Michael | |
Skelin, Maša | 29565 |
Jevšek, Marko | 22403 |
Fink, Heidrun | |
Rupnik, Marjan | 12266 |
Walther, Diego J. |
Vir: Osebne bibliografije
in: SICRIS
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