Abstract
The recent demonstration that pancreatic α cells can be continuously regenerated and converted into β-like cells upon ectopic expression of Pax4 opened new avenues of research in the endocrine cell differentiation and diabetes fields. To determine whether such plasticity was also shared by δ cells, we generated and characterized transgenic animals that express Pax4 specifically in somatostatin-expressing cells. We demonstrate that the ectopic expression of Pax4 in δ cells is sufficient to induce their conversion into functional β-like cells. Importantly, this conversion induces compensatory mechanisms involving the reactivation of endocrine developmental processes that result in dramatic β-like cell hyperplasia. Importantly, these β-like cells are functional and can partly reverse the consequences of chemically induced diabetes.
© 2017 Druelle et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation
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Cell Transdifferentiation / genetics
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / genetics*
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / therapy
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Ectopic Gene Expression*
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Genetic Therapy / methods
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Glucagon / biosynthesis
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Glucagon / genetics
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Insulin / biosynthesis
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Insulin / genetics
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Insulin-Secreting Cells / cytology
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Insulin-Secreting Cells / metabolism*
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Male
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Mice
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Mice, Transgenic
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Paired Box Transcription Factors / genetics*
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Paired Box Transcription Factors / metabolism
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Somatostatin / biosynthesis
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Somatostatin / genetics
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Somatostatin-Secreting Cells / cytology
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Somatostatin-Secreting Cells / metabolism*
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Streptozocin
Substances
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Homeodomain Proteins
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Insulin
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Paired Box Transcription Factors
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Pax4 protein, mouse
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Somatostatin
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Streptozocin
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Glucagon