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Review: Diabetes, Obesity and Metabolism

Out of the four pancreatic islet endocrine cell types, β-cells are arguably the most important. Indeed, their physical or functional loss is one of the hallmarks of diabetes, a group of metabolic diseases characterized by the persistence of high unregulated blood glucose levels, and estimated to affect 592 million adults by 2035. The extent of β-cell loss differs in the different forms of the disease, even in diabetes resulting from autoimmunity.

β-Cell number have always been thought to remain stable after birth, and undergo only minor variations throughout life. However, multiple studies have shown that β-cell mass dynamically adjusts when metabolic demand increases or upon injury, at least in rodents but likely in humans as well. Under most circumstances, proliferation of pre-existing β-cells is the major driver of postnatal islet cell expansion. Neogenesis, ie, differentiation of undefined adult progenitors or stem cells, has also been proposed, but the identity and nature of such precursor cells remain controversial. Interestingly, recent studies report that extra-islet (acinar and ductal) and intra-islet (α- or δ-) cells contribute to β-cell mass restoration under stress conditions by reprogramming into insulin production. These observations have been possible thanks to the development of different in vivo cell lineage tracing tools, which allow conditional or inducible [through doxycycline (DOX) or tamoxifen (TAM) administration] “tagging” of specific cell types in order to track their fate changes.

Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas.

Continue your reading  here:

Stress-induced adaptive islet cell identity changes

Authors: Valentina Cigliola, Fabrizio Thorel, Simona Chera and Pedro Herrera

Journal: Diabetes, Obesity and Metabolism  (2016), pp. 87-96

DOI information: 10.1111/dom.12726

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Conferences and talks

19/04/2017 Inauguration of KG Jebsen Center for Diabetes Research, Bergen
25/04/2017 The Christie Conference, Grieghallen Bergen (Christiekonferansen 2017)
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