Cargando…

Laminin matrix regulates beta-cell FGFR5 expression to enhance glucose-stimulated metabolism

We previously showed that pancreatic beta-cells plated on laminin matrix express reduced levels of FGFR1, a receptor linked to beta-cell metabolism and differentiation. Due to recent evidence that adult beta-cells also express FGFR5, a co-receptor for FGFR1, we now aim to determine the effect of lam...

Descripción completa

Detalles Bibliográficos
Autores principales: Pal, Vidhant, Wang, Yufeng, Regeenes, Romario, Kilkenny, Dawn M., Rocheleau, Jonathan V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005713/
https://www.ncbi.nlm.nih.gov/pubmed/35414066
http://dx.doi.org/10.1038/s41598-022-09804-7
Descripción
Sumario:We previously showed that pancreatic beta-cells plated on laminin matrix express reduced levels of FGFR1, a receptor linked to beta-cell metabolism and differentiation. Due to recent evidence that adult beta-cells also express FGFR5, a co-receptor for FGFR1, we now aim to determine the effect of laminin on FGFR5 expression and consequent effects on beta-cell metabolism. Using a genetically encoded sensor for NADPH/NADP(+) redox state (Apollo-NADP(+)), we show overexpression of FGFR5 enhances glucose-stimulated NADPH metabolism in beta-cell lines as well as mouse and human beta-cells. This enhanced response was accompanied by increased insulin secretion as well as increased expression of transcripts for glycolytic enzymes (Glucokinase/GCK, PKM2) and the functional maturity marker Urocortin 3 (UCN3). Culturing beta-cells on laminin matrix also stimulated upregulation of endogenous FGFR5 expression, and similarly enhanced beta-cell glucose-stimulated NADPH-metabolism as well as GCK and PKM2 transcript expression. The metabolism and transcript responses triggered by laminin were disrupted by R5ΔC, a truncated receptor isoform that inhibits the FGFR5/FGFR1 signaling complex. Collectively these data reveal that beta-cells respond to laminin by increasing FGFR5 expression to enhance beta-cell glucose metabolism.