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Diabetes. 2017 May;66(5):1293-1300. doi: 10.2337/db16-0887. Epub 2017 Feb 21.

Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo.

Author information

1
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan matsuoka@endmet.med.osaka-u.ac.jp.
2
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
3
Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
4
Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Geneva, Switzerland.
5
Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan.
6
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN.

Abstract

Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin-positive cells. Here we have generated transgenic mice conditionally expressing the islet β-cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3-positive progenitors and the later glucagon-positive α-cell population into β-cells. Mafa was found to both potentiate the ability of Pdx1 to induce β-cell formation from Ngn3-positive endocrine precursors and enable Pdx1 to produce β-cells from α-cells. These results provide valuable insight into the fundamental mechanisms influencing islet cell plasticity in vivo.

PMID:
28223284
PMCID:
PMC5399608
DOI:
10.2337/db16-0887
[Indexed for MEDLINE]
Free PMC Article

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