ZFIN ID: ZDB-PUB-171224-2
Metformin, beta-cell development, and novel processes following beta-cell ablation in zebrafish
Wyett, G., Gibert, Y., Ellis, M., Castillo, H.A., Kaslin, J., Aston-Mourney, K.
Date: 2017
Source: Endocrine   59(2): 419-425 (Journal)
Registered Authors: Gibert, Yann, Kaslin, Jan
Keywords: Beta-cell, Development, Diabetes, Metformin, Regeneration, Zebrafish
MeSH Terms:
  • Animals
  • Cell Size/drug effects
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/drug effects*
  • Glucagon/genetics
  • Glucagon/metabolism
  • Hypoglycemic Agents/pharmacology*
  • Insulin-Secreting Cells/drug effects*
  • Insulin-Secreting Cells/metabolism
  • Metformin/pharmacology*
  • Somatostatin/genetics
  • Somatostatin/metabolism
  • Zebrafish
PubMed: 29274062 Full text @ Endocrine
Type 1 and 2 diabetes are characterized by a loss of insulin-producing beta-cells. Current treatments help maintain blood glucose levels but cannot provide a cure. As such, a vital target for the cure of diabetes is a way to restore beta-cell mass. The drug metformin can protect cultured beta-cells/islets from hyperglycemia-induced dysfunction and death. Further, treatment of pregnant mice with metformin results in an enhanced beta-cell fraction in the embryos; however, whether this occurs via a direct effect is unknown.
We utilized the external embryogenesis of the zebrafish to determine the direct effect of metformin treatment on the pancreas of the developing embryo and following beta-cell ablation.
During development metformin did not alter beta-cell or alpha-cell mass but had a small effect to increase delta-cell mass as measured by in situ hybridization. Further metformin significantly increased beta-cell number. Following beta-cell ablation, both glucagon and somatostatin expression were upregulated (>2-fold). Additionally, while metformin showed no effect to alter beta-cell mass or number, somatostatin expression was further increased (>5-fold).
We showed that direct exposure to metformin during embryogenesis does not increase insulin-expressing area but does increase beta-cell number. Further, we identified novel consequences of beta-cell ablation to alter the expression of other pancreatic hormones that were enhanced by metformin. Therefore, this study provides a greater understanding of the beta-cell development/regenerative processes and the effect of metformin, bringing us closer to identifying how to increase beta-cells in humans.