Glucose induces an autocrine activation of the Wnt/beta-catenin pathway in macrophage cell lines.
The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin-mediated beta-catenin degradation. This results in the accumulation and subsequent nuclear translocation of beta-catenin, which induces the expression of a number of genes involved in growth, differentiation and metabolism. The mechanisms regulating the Wnt signalling pathway in the physiological context is still not fully understood. In the present study we provide evidence that changes in glucose levels within the physiological range can acutely regulate the levels of beta-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In particular we find that glucose induces these effects by promoting an autocrine activation of Wnt signalling that is mediated by the hexosamine pathway and changes in N-linked glycosylation of proteins. These studies reveal that the Wnt/beta-catenin system is a glucose-responsive signalling system and as such is likely to play a role in pathways involved in sensing changes in metabolic status.
Anagnostou
Sasha H
SH
Department of Molecular Medicine and Pathology and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1142, New Zealand.
Shepherd
Peter R
PR
D000818:Animals; D060466:Axin Protein; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008113:Liver Neoplasms; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology
D060466:Axin Protein; C111729:Axin2 protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D012313:RNA; D005947:Glucose