SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Liu Shuwen)
 

Sökning: WFRF:(Liu Shuwen) > GLP-1 Receptor Acti...

  • He, ShijunSouthern Medical University, Guangzhou, China (författare)

GLP-1 Receptor Activation Abrogates β-Cell Dysfunction by PKA Cα-Mediated Degradation of Thioredoxin Interacting Protein

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019-10-25
  • Frontiers Media SA,2019
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:hh-48370
  • https://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-48370URI
  • https://doi.org/10.3389/fphar.2019.01230DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Glucagon-like peptide 1 receptor (GLP-1R) agonist (Exendin-4) is a well-known agent used to improve β-cell dysfunctions via protein kinase A (PKA), but the detailed downstream molecular mechanisms are still elusive. We have now found that PKA Cα mediated- TXNIP phosphorylation and degradation played a vital role in the β-cell protective role of exendin-4. After PKA activator (Exendin-4 or FSK) treatment, PKA Cα could directly interact with TXNIP by bimolecular fluorescence complementation and Co-IP assays in INS-1 cells. And PKA Cα overexpression decreased TXNIP level, whereas TXNIP level was largely increased in PKA Cα-KO β-cells by CRISPR-Cas9. Interestingly, TXNIP overexpression or PKA Cα-KO has impaired β-cell functions, including loss of insulin secretion and activation of inflammation. PKA Cα directly phosphorylated TXNIP at Ser307 and Ser308 positions, leading to its degradation via activation of cellular proteasome pathway. Consistent with this observation, TXNIP (S307/308A) mutant resisted the degradation effects of PKA Cα. However, exendin-4 neither affected TXNIP level in TXNIP (S307/308A) mutant overexpressed β-cells nor in PKA Cα-KO β-cells. Moreover, exendin-4 treatment reduced the inflammation gene expression in TXNIP overexpressed β-cells, but exendin-4 treatment has no effect on the inflammation gene expression in TXNIP (S307/308A) overexpressed β-cells. In conclusion, our study reveals the integral role of PKA Cα/TXNIP signaling in pancreatic β-cells and suggests that PKA Cα-mediated TXNIP degradation is vital in β-cell protective effects of exendin-4.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Wu, WenyuSun Yat-sen University, Guangzhou, China (författare)
  • Wan, YihongSouthern Medical University, Guangzhou, China (författare)
  • Nandakumar, Kutty Selva,1965-Southern Medical University, Guangzhou, China(Swepub:hh)kutnam (författare)
  • Cai, XiuchaoSouthern Medical University, Guangzhou, China (författare)
  • Tang, XiaodongSouthern Medical University, Guangzhou, China (författare)
  • Liu, ShuwenSouthern Medical University, Guangzhou, China: Southern Medical University, Foshan, China (författare)
  • Yao, XingangSouthern Medical University, Guangzhou, China (författare)
  • Southern Medical University, Guangzhou, ChinaSun Yat-sen University, Guangzhou, China (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Frontiers in Pharmacology: Frontiers Media SA101663-9812

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy