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Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology

Masjkur, Jimmy; Poser, Steven W.; Nikolakopoulou, Polyxeni; Chrousos, George; McKay, Ronald D.; Bornstein, Stefan R.; Jones, Peter M.; Androutsellis-Theotokis, Andreas

Authors

Jimmy Masjkur

Steven W. Poser

Polyxeni Nikolakopoulou

George Chrousos

Ronald D. McKay

Stefan R. Bornstein

Peter M. Jones

Andreas Androutsellis-Theotokis



Abstract

Loss of insulin-producing pancreatic islet β-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as “on” or “off” but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as “off” or “low” may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways.

Journal Article Type Article
Publication Date Feb 1, 2016
Journal Diabetes
Print ISSN 0012-1797
Electronic ISSN 1939-327X
Publisher American Diabetes Association
Peer Reviewed Peer Reviewed
Volume 65
Issue 2
APA6 Citation Masjkur, J., Poser, S. W., Nikolakopoulou, P., Chrousos, G., McKay, R. D., Bornstein, S. R., …Androutsellis-Theotokis, A. (2016). Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology. Diabetes, 65(2), doi:10.2337/db15-1099
DOI https://doi.org/10.2337/db15-1099
Publisher URL http://diabetes.diabetesjournals.org/content/65/2/314
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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