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Diabetologia
Published in: Diabetologia 9/2016

01-09-2016 | Article

A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia

Authors: Marie Lemper, Sofie De Groef, Geert Stangé, Luc Baeyens, Harry Heimberg

Published in: Diabetologia | Issue 9/2016

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Abstract

Aims/hypothesis

When the beta cell mass or function declines beyond a critical point, hyperglycaemia arises. Little is known about the potential pathways involved in beta cell rescue. As two cytokines, epidermal growth factor (EGF) and ciliary neurotrophic factor (CNTF), restored a functional beta cell mass in mice with long-term hyperglycaemia by reprogramming acinar cells that transiently expressed neurogenin 3 (NGN3), the current study assesses the effect of these cytokines on the functional beta cell mass after an acute chemical toxic insult.

Methods

Glycaemia and insulin levels, pro-endocrine gene expression and beta cell origin, as well as the role of signal transducer and activator of transcription 3 (STAT3) signalling, were assessed in EGF+CNTF-treated mice following acute hyperglycaemia.

Results

The mice were hyperglycaemic 1 day following i.v. injection of the beta cell toxin alloxan, when the two cytokines were applied. One week later, 68.6 ± 4.6% of the mice had responded to the cytokine treatment and increased their insulin+ cell number to 30% that of normoglycaemic control mice, resulting in restoration of euglycaemia. Although insulin− NGN3+ cells appeared following acute EGF+CNTF treatment, genetic lineage tracing showed that the majority of the insulin+ cells originated from pre-existing beta cells. Beta cell rescue by EGF+CNTF depends on glycaemia rather than on STAT3-induced NGN3 expression in acinar cells.

Conclusions/interpretation

In adult mice, EGF+CNTF allows the rescue of beta cells in distress when treatment is given shortly after the diabetogenic insult. The rescued beta cells restore a functional beta cell mass able to control normal blood glucose levels. These findings may provide new insights into compensatory pathways activated early after beta cell loss.
Appendix
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Metadata
Title
A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia
Authors
Marie Lemper
Sofie De Groef
Geert Stangé
Luc Baeyens
Harry Heimberg
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 9/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4023-3

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