Wnt signalling at the crossroads of nutritional regulation.
The ability to sense and respond to nutritional cues is among the most fundamental processes that support life in living organisms. At the cellular level, a number of biochemical mechanisms have been proposed to mediate cellular glucose sensing. These include ATP-sensitive potassium channels, AMP-activated protein kinase, activation of PKC (protein kinase C), and flux through the hexosamine pathway. Less well known is how cellularly heterogenous organs couple nutrient availability to prioritization of cell autonomous functions and appropriate growth of the entire organ. Yet what is clear is that when such mechanisms fail or become inappropriately active they can lead to dire consequences such as diabetes, metabolic syndromes, cardiovascular diseases and cancer. In this issue of the Biochemical Journal, Anagnostou and Shepherd report the identification of an important link between cellular glucose sensing and the Wnt/beta-catenin signalling pathway in macrophages. Their data strongly indicate that the Wnt/beta-catenin pathway of Wnt signalling is responsive to physiological concentrations of nutrients but also suggests that that this system could be inappropriately activated in the diabetic (hyperglycaemic) or other metabolically compromised pathological states. This opens the exciting possibility that organ-selective modulation of Wnt signalling may become an attractive therapeutic target to treat these diseases.
Sethi
Jaswinder K
JK
Department of Clinical Biochemistry, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Addenbrooke's Treatment Centre, Addenbrooke's Hospital Box 289, Hills Road, Cambridge CB20QQ, UK. jks30@cam.ac.uk
Vidal-Puig
Antonio J
AJ
D000117:Acetylglucosamine / Q000502:physiology; D060466:Axin Protein; D019938:Cyclin D1 / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000502:physiology; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
C491761:AXIN2 protein, human; D060466:Axin Protein; D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D005947:Glucose; D000117:Acetylglucosamine