Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Beta-Cell Regeneration in Zebrafish; Metformin and Consequences for Alpha and Delta Cells (#209)

Georgia Wyett 1 , Yann Gibert 1 , Megan Ellis 1 , Kathryn Aston-Mourney 1
  1. Deakin University, Waurn Ponds, VIC, Australia

*Wyett and Gibert contributed equally


Type 1 and 2 Diabetes are characterised by a complete or relative lack of insulin.  Current treatments help maintain blood glucose levels but can’t provide a cure. As such, a vital target for the cure of diabetes is a way to restore beta-cell mass.

We have shown that the drug metformin can protect beta-cells from hyperglycaemia-induced dysfunction and death. Further, another study showed that treatment of pregnant mice with metformin resulted in enhanced pancreatic progenitors and beta-cell fraction in the embryos (Gregg et al. Diabetologia, 2014). Thus metformin may be able to enhance beta-cell mass however, whether this occurs via a direct effect on the embryo is unknown.

In the current study, we utilised the external embryogenesis of the zebrafish, to determine the direct effect of metformin on the pancreas of the developing embryo and following beta-cell ablation.

During development metformin did not alter beta- or alpha-cell mass but it had a small effect to increase somatostatin expression and delta-cell mass.  Following beta-cell ablation, both glucagon and somatostatin expression were upregulated (>2-fold) early however glucagon expression normalised and somatostatin expression decreased later.  Further, while metformin showed no effect to alter beta-cell mass, somatostatin expression was further increased to more than 5 times of normal.

Overall we showed that direct exposure to metformin during embryogenesis did not alter beta-cell mass indicating that the previously seen effects may be due to effects on the mother resulting in increased beta-cells in the embryos. Further, we identified novel consequences of beta-cell ablation to alter the expression of other pancreatic endocrine hormones which can be enhanced by metformin.  Therefore, this study has provided a greater understanding of the beta-cell development/regenerative processes and how metformin can influence these; bringing us closer to identifying a way to increase beta-cells in humans.