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 |
|---|---|
| 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
Cite this
}
Metformin, beta-cell development, and novel processes following beta-cell ablation in zebrafish. / Wyett, Georgia; Gibert, Yann; Ellis, Megan; Castillo, Hozana A.; Kaslin, Jan; Aston-Mourney, Kathryn.
In: Endocrine, Vol. 59, No. 2, 01.02.2018, p. 419-425.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Metformin, beta-cell development, and novel processes following beta-cell ablation in zebrafish
AU - Wyett, Georgia
AU - Gibert, Yann
AU - Ellis, Megan
AU - Castillo, Hozana A.
AU - Kaslin, Jan
AU - Aston-Mourney, Kathryn
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Beta-cell
KW - Development
KW - Diabetes
KW - Metformin
KW - Regeneration
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85038849346&partnerID=8YFLogxK
U2 - 10.1007/s12020-017-1502-3
DO - 10.1007/s12020-017-1502-3
M3 - Article
AN - SCOPUS:85038849346
VL - 59
SP - 419
EP - 425
JO - Endocrine
JF - Endocrine
SN - 1355-008X
IS - 2
ER -