Back to Search
Start Over
A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.
- Source :
-
Diabetologia [Diabetologia] 2016 Sep; Vol. 59 (9), pp. 1948-58. Date of Electronic Publication: 2016 Jun 18. - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Alloxan toxicity
Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Blood Glucose drug effects
Insulin metabolism
Male
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Signal Transduction drug effects
Ciliary Neurotrophic Factor therapeutic use
Epidermal Growth Factor therapeutic use
Hyperglycemia drug therapy
Insulin-Secreting Cells drug effects
Insulin-Secreting Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0428
- Volume :
- 59
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 27318836
- Full Text :
- https://doi.org/10.1007/s00125-016-4023-3