Evidence map›Paper›PMID 26693711›Full record

ArticleDiabetologia2016

Hyperglycaemia attenuates in vivo reprogramming of pancreatic exocrine cells to beta cells in mice.

Claudia Cavelti-Weder, Weida Li, Adrian Zumsteg, Marianne Stemann-Andersen, Yuemei Zhang, Takatsugu Yamada, Max Wang, Jiaqi Lu, Agnes Jermendy, Yong Mong Bee and 3 more

Abstract read
In one paragraph

Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Review
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  3. Article
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  6. Review
  7. Regenerative medicine of pancreatic islets.World journal of gastroenterology · 2020
    Review
  8. Review
  9. Aldh1b1 expression defines progenitor cells in the adult pancreas and is required for Kras-induced pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  10. Regenerative medicine and cell-based approaches to restore pancreatic function.Nature reviews. Gastroenterology & hepatology · 2017
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells.Therapeutic advances in endocrinology and metabolism · 2016
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Claudia Cavelti-WederSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Weida LiTranslational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Life Sciences and Technology, Shanghai, The People's Republic of China.
Adrian ZumstegDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 258C, 7 Divinity Ave, Cambridge, MA, 02138, USA.
Marianne Stemann-AndersenSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Yuemei ZhangDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 258C, 7 Divinity Ave, Cambridge, MA, 02138, USA.
Takatsugu YamadaSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Max WangDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 258C, 7 Divinity Ave, Cambridge, MA, 02138, USA.
Jiaqi LuDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 258C, 7 Divinity Ave, Cambridge, MA, 02138, USA.
Agnes JermendySection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Yong Mong BeeSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Susan Bonner-WeirSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Gordon C WeirSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard University, Boston, MA, USA.
Qiao ZhouDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 258C, 7 Divinity Ave, Cambridge, MA, 02138, USA. qiao_zhou@harvard.edu.

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Regenerating Beta Cells by Lineage ReprogrammingU01DK089536 · NIDDK · HARVARD UNIVERSITY · PI MELTON, DOUGLAS A · 2010 to 2014
$2.8M
Physiological Factors Driving Maturation of Neonatal Beta CellsR01DK093909 · NIDDK · JOSLIN DIABETES CENTER · PI BONNER-WEIR, SUSAN · 2011 to 2015
$1.8M
Phenotypic Analysis of Young and Old Beta CellsR01DK066056 · NIDDK · JOSLIN DIABETES CENTER · PI BONNER-WEIR, SUSAN · 2005 to 2008
$1.1M
Molecular Control of Pancreatic Beta Cell ReprogrammingR00DK077445 · NIDDK · HARVARD UNIVERSITY · PI ZHOU, QIAO JOE · 2009 to 2011
$739k
NIDDK NIH HHS DK 093909NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R00 DK077445NIDDK NIH HHS R01 DK 066056NIDDK NIH HHS R01 DK066056NIDDK NIH HHS R01 DK093909NIDDK NIH HHS U01 DK089536
6 · The paper itself

Abstract

aims/hypothesisReprogramming of pancreatic exocrine to insulin-producing cells by viral delivery of the genes encoding transcription factors neurogenin-3 (Ngn3), pancreas/duodenum homeobox protein 1 (Pdx1) and MafA is an efficient method for reversing diabetes in murine models. The variables that modulate reprogramming success are currently ill-defined.

methodsHere, we assess the impact of glycaemia on in vivo reprogramming in a mouse model of streptozotocin-induced beta cell ablation, using subsequent islet transplantation or insulin pellet implantation for creation of groups with differing levels of glycaemia before viral delivery of transcription factors.

resultsWe observed that hyperglycaemia significantly impaired reprogramming of exocrine to insulin-producing cells in their quantity, differentiation status and function. With hyperglycaemia, the reprogramming of acinar towards beta cells was less complete. Moreover, inflammatory tissue changes within the exocrine pancreas including macrophage accumulation were found, which may represent the tissue's response to clear the pancreas from insufficiently reprogrammed cells. CONCLUSIONS/

interpretationOur findings shed light on normoglycaemia as a prerequisite for optimal reprogramming success in a diabetes model, which might be important in other tissue engineering approaches and disease models, potentially facilitating their translational applications.

Indexed as

AnimalsCellular ReprogrammingHyperglycemiaInsulin-Secreting CellsIn Vitro TechniquesMaleMicePancreas, ExocrineDiabetesExocrine to beta cell reprogrammingHyperglycaemia

Identifiers

PMID26693711
PMCPMC4744133

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.