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

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 unde...

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Main Authors: Masjkur, Jimmy, Poser, Steven W., Nikolakopoulou, Polyxeni, Chrousos, George, McKay, Ronald D., Bornstein, Stefan R., Jones, Peter M., Androutsellis-Theotokis, Andreas
Format: Article
Published: American Diabetes Association 2016
Online Access:https://eprints.nottingham.ac.uk/42831/
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author Masjkur, Jimmy
Poser, Steven W.
Nikolakopoulou, Polyxeni
Chrousos, George
McKay, Ronald D.
Bornstein, Stefan R.
Jones, Peter M.
Androutsellis-Theotokis, Andreas
author_facet Masjkur, Jimmy
Poser, Steven W.
Nikolakopoulou, Polyxeni
Chrousos, George
McKay, Ronald D.
Bornstein, Stefan R.
Jones, Peter M.
Androutsellis-Theotokis, Andreas
author_sort Masjkur, Jimmy
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-428312020-05-04T20:04:11Z https://eprints.nottingham.ac.uk/42831/ 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 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. American Diabetes Association 2016-02 Article PeerReviewed Masjkur, Jimmy, Poser, Steven W., Nikolakopoulou, Polyxeni, Chrousos, George, McKay, Ronald D., Bornstein, Stefan R., Jones, Peter M. and Androutsellis-Theotokis, Andreas (2016) Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology. Diabetes, 65 (2). pp. 314-330. ISSN 1939-327X http://diabetes.diabetesjournals.org/content/65/2/314 doi:10.2337/db15-1099 doi:10.2337/db15-1099
spellingShingle Masjkur, Jimmy
Poser, Steven W.
Nikolakopoulou, Polyxeni
Chrousos, George
McKay, Ronald D.
Bornstein, Stefan R.
Jones, Peter M.
Androutsellis-Theotokis, Andreas
Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title_full Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title_fullStr Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title_full_unstemmed Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title_short Endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
title_sort endocrine pancreas development and regeneration: noncanonical ideas from neural stem cell biology
url https://eprints.nottingham.ac.uk/42831/
https://eprints.nottingham.ac.uk/42831/
https://eprints.nottingham.ac.uk/42831/