1. A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.
- Author
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Lemper, Marie, Groef, Sofie, Stangé, Geert, Baeyens, Luc, and Heimberg, Harry
- 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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