Projects per year
Abstract
Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.
Original language | English |
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Pages (from-to) | 419-425 |
Number of pages | 7 |
Journal | Endocrine |
Volume | 59 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2018 |
Keywords
- Beta-cell
- Development
- Diabetes
- Metformin
- Regeneration
- Zebrafish
Projects
- 1 Finished
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The role of immune cells and the transcription factor Hmga1 in boosting neural regeneration
Kaslin, J. (Primary Chief Investigator (PCI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/14 → 31/12/16
Project: Research
Equipment
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Monash Micro Imaging (MMI)
Firth, S. (Manager), Fulcher, A. (Operator), Chernyavskiy, O. (Operator), Rzeszutek, M. (Other), Potter, D. (Manager), Hilsenstein, V. (Operator), Nunez-Iglesias, J. (Other), Cody, S. (Manager), Carmichael, I. (Operator), Kouskousis, B. (Other), Creed, S. (Manager) & Ballerin, G. (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility