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Pathophysiological aspects of Wnt-signaling in endocrine disease

Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany

(Correspondence should be addressed to S Schinner; Email: sven.schinner{at}uni-duesseldorf.de)

Abstract

Wnt-signaling has recently been identified as a regulator of a number of endocrine functions in health and disease in addition to its original attribution to developmental biology. Wnts are extracellular ligands on frizzled receptors and on lipoprotein receptor-related protein co-receptors. Ligand binding leads eventually to the activation of intracellular signaling cascades; based on the involvement of the transcriptional co-activator β-catenin it can be distinguished between canonical (i.e. β-catenin) and non-canonical Wnt-signaling. Recent studies revealed that canonical Wnt-signaling regulates the function of endocrine organs and contributes to a number of endocrine disorders. In this review, we would like to focus on a) recent mechanistic data on Wnts in pancreatic β-cell function; b) human genetic studies on Wnt signaling in type 2 diabetes mellitus; c) crosstalk between adipocytes and endocrine cells through Wnt-signaling molecules (with a focus on the role of Wnt-signaling in adrenocortical cells).