Hyperglycaemia Attenuates in Vivo Reprogramming of Pancreatic Exocrine Cells to Beta Cells in Mice

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2015 Dec 24

PMID 26693711

Citations 17

Authors

Claudia Cavelti-Weder

Weida Li

Adrian Zumsteg

Marianne Stemann-Andersen

YueMei Zhang

Takatsugu Yamada

Max Wang

Jiaqi Lu

Agnes Jermendy

Yong Mong Bee

Susan Bonner-Weir

Gordon C Weir

Qiao Zhou

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Reprogramming 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.

Methods: Here, 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.

Results: We 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/interpretation: Our 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.

Citing Articles

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EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells.

dordevic M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunovic V, Tolic A Front Endocrinol (Lausanne). 2023; 14:1134478.

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Cellular Reprogramming and Its Potential Application in Alzheimer's Disease.

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Kaneto H, Kimura T, Shimoda M, Obata A, Sanada J, Fushimi Y Biomedicines. 2022; 10(4).

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Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.

Spears E, Serafimidis I, Powers A, Gavalas A Front Endocrinol (Lausanne). 2021; 12:722250.

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