Protein kinase-D1 and downstream signaling mechanisms involved in GLUT4 translocation in cardiac muscle

Şimşek Papur Ö., Glatz J., Luiken J.


  • Publication Type: Article / Review
  • Volume: 1 Issue: 1
  • Publication Date: 2024
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1-2
  • Dokuz Eylül University Affiliated: Yes


Th e Ser/Th r kinase pr otein kinase -D1 (PKD1) is involved in indu ction of va r iou s cell phys i olo g ica l processe s in th e hear t such as myocellula r hype rtr oph y an d inflammation , whic h ma y turn ma ladaptive du rin g long -term stim ulation . Of sp ecial inte res t is a ke y role of PKD1 in th e re g ulation of ca rdiac su bstrate meta b olism . Gl ucose an d fatt y acid s ar e th e most impo rtant su bstrate s fo r ca rdiac energy pr ovision , an d th e rati o at whic h they ar e ut i - lize d dete rmine s th e health st atu s of th e heart. Ca rdiac gl ucose uptake is mainly re g ulate d by transl ocation of th e gl ucose tran sporter GLUT 4 from intr ace llula r stores (e ndosomes) to th e sa rcolemma, an d fatt y acid uptake vi a a pa ralle l transl ocation of fatt y acid tran sporter CD36 from endosome s to th e sa rcolemma. PKD1 is involved in th e re g ulation of GLUT 4 transl ocation , bu t no t CD36 transl ocation , gi vin g it th e abilit y to mo d ulate gl ucose uptake withou t affectin g fatt y acid uptake , thereb y alte rin g th e ca rdiac su bstrate ba lance . PKD1 woul d ther efore serv e as an attractive ta rge t to co mba t ca rdiac metaboli c di sease s with a tilted su bstrate ba lance , such as di abeti c ca r - diom yop athy. Ho wever , PKD1 activation also elicit s ca rdiac hype rtr oph y an d inflammation . Ther efore , identifi - cation of th e events upstream an d downstream of PKD1 ma y pr ovide superior ther ape uti c ta rgets to alte r th e ca r - diac su bstrate ba lance . Recent studie s have identified th e lipi d kinase phosphatidyl ino s ito l 4 -kinase II I β (PI4KI - II β ) as si gna lin g hu b downstream of PKD1 to sele ctively stim ulate GLUT 4 -mediated myocardial gl ucose uptake withou t indu cin g hype rtr ophy. Take n together , th e PKD1 si gna lin g pathwa y serves a pi votal role in ca rdiac gl u - cose meta b olism an d is a promisin g ta rge t to sele ctively mo d ulate gl ucose uptake in ca rdiac di sease .