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Important Signals Identified for the Targeted Development and Regeneration of Beta Cells

A collaborative study by an international team of scientists published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS) shows that the Notch signaling pathway is essential for the formation of insulin-producing beta cells. The results of the study indicate new starting points for the treatment of diabetes mellitus based on beta cell replacement therapy and the regeneration of the islets of Langerhans.

 

In the current issue of the prestigious journal Proceedings of the National Academy of Sciences (PNAS), scientists show that Mind bomb1, a regulator for the Notch signaling pathway*, is crucial for the proper physiological development of beta cells during embryonic development. Thus, the significance of the Notch signaling pathway goes beyond the mere maintenance of the progenitor cells. The findings are essential to enable in vitro differentiation of beta cells from their progenitor cells and thus in the future to develop cell replacement therapies for people with diabetes or to stimulate the formation of new beta cells in adults. The study was carried out in collaboration with the Danish Stem Cell Center with NovoNordisk. In addition, Vanderbilt University in the U.S., Kyoto University in Japan, Seoul University in South Korea and Helmholtz Zentrum München, a partner in the German Center for Diabetes Research, were involved.

A future-oriented model
Professor Heiko Lickert, director of the Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München, and his team made a contribution that was critical to the success of the project: They succeeded in generating a mouse strain in which the Notch signaling pathway in the pancreas can be deactivated. Through the targeted activation and deactivation of genes during organ development, the scientists can study in detail which signals and factors regulate the development of the beta cells. Thus, this model will contribute beyond the current study to concrete medical advances in the field of regenerative medicine: “Our findings are an important step in order to stimulate the formation of new beta cells and in the long-term to enable the development of cell replacement therapies and the regeneration of beta cells in patients with diabetes,” said Lickert.

 

Further Information
Background
* The Notch signaling pathway controls important processes in the embryonic development of mammals and humans. Among other things, it is involved in the formation of pancreatic beta cells.

Original publication:
Horn S. et al.(2012) Mind bomb 1 is required for pancreatic β-cell formation, PNAS April 23, 2012, doi: 10.1073/pnas.1203605109 (Abstract)