[HTML][HTML] Pharmacological induction of pancreatic islet cell transdifferentiation: relevance to type I diabetes

R Piran, SH Lee, CR Li, A Charbono, LM Bradley… - Cell death & …, 2014 - nature.com
R Piran, SH Lee, CR Li, A Charbono, LM Bradley, F Levine
Cell death & disease, 2014nature.com
Abstract Type I diabetes (T1D) is an autoimmune disease in which an immune response to
pancreatic β-cells results in their loss over time. Although the conventional view is that this
loss is due to autoimmune destruction, we present evidence of an additional phenomenon in
which autoimmunity promotes islet endocrine cell transdifferentiation. The end result is a
large excess of δ-cells, resulting from α-to β-to δ-cell transdifferentiation. Intermediates in the
process of transdifferentiation were present in murine and human T1D. Here, we report that …
Abstract
Type I diabetes (T1D) is an autoimmune disease in which an immune response to pancreatic β-cells results in their loss over time. Although the conventional view is that this loss is due to autoimmune destruction, we present evidence of an additional phenomenon in which autoimmunity promotes islet endocrine cell transdifferentiation. The end result is a large excess of δ-cells, resulting from α-to β-to δ-cell transdifferentiation. Intermediates in the process of transdifferentiation were present in murine and human T1D. Here, we report that the peptide caerulein was sufficient in the context of severe β-cell deficiency to induce efficient induction of α-to β-to δ-cell transdifferentiation in a manner very similar to what occurred in T1D. This was demonstrated by genetic lineage tracing and time course analysis. Islet transdifferentiation proceeded in an islet autonomous manner, indicating the existence of a sensing mechanism that controls the transdifferentiation process within each islet. The finding of evidence for islet cell transdifferentiation in rodent and human T1D and its induction by a single peptide in a model of T1D has important implications for the development of β-cell regeneration therapies for diabetes.
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