ArticleDiabetologia2014
Exposure of mouse embryonic pancreas to metformin enhances the number of pancreatic progenitors.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.Diabetic medicine : a journal of the British Diabetic Association · 2024Pooled it
- Review
- Epigenetic modulation of cell fate during pancreas development.Trends in developmental biology · 2023Article
- Metformin induces mitochondrial remodeling and differentiation of pancreatic progenitor cells into beta-cells by a potential mechanism including suppression of the T1R3, PLCβ2, cytoplasmic CaJournal of physiology and biochemistry · 2022Article
- Placental mTOR Signaling and Sexual Dimorphism in Metabolic Health across the Lifespan of Offspring.Children (Basel, Switzerland) · 2021Review
- Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules.Pharmaceutics · 2021Article
- Developmental effects ofTrends in developmental biology · 2021Article
- Article
- Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner.American journal of physiology. Endocrinology and metabolism · 2020Article
- Role of nutrient-driven O-GlcNAc-post-translational modification in pancreatic exocrine and endocrine islet development.Development (Cambridge, England) · 2020Article
- Comparative effects of glibenclamide, metformin and insulin on fetal pancreatic histology and maternal blood glucose in pregnant streptozotocin-induced diabetic rats.African health sciences · 2019Article
- Metformin Reduces Lipotoxicity-Induced Meta-Inflammation inJournal of diabetes research · 2019Article
- Metformin from mother to unborn child - Are there unwarranted effects?EBioMedicine · 2018Review
- Gestational exposure to metformin programs improved glucose tolerance and insulin secretion in adult male mouse offspring.Scientific reports · 2018Article
- Metformin, beta-cell development, and novel processes following beta-cell ablation in zebrafish.Endocrine · 2018Article
- Metformin in the management of diabetes during pregnancy and lactation.Drugs in context · 2018Review
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisDeveloping beta cells are vulnerable to nutrient environmental signals. Early developmental processes that alter the number of pancreatic progenitors can determine the number of beta cells present at birth. Metformin, the most widely used oral agent for treating diabetes, alters intracellular energy status in part by increasing AMP-activated protein kinase (AMPK) signalling. This study examined the effect of metformin on developing pancreas and beta cells.
methodsPancreatic rudiments from CD-1 mice at embryonic day 13.0 (E13.0) were cultured with metformin, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an AMPK activator) or vehicle control in vitro. In another set of studies, pregnant C57BL/6 mice were treated with metformin throughout gestation. Embryonic (E14.0) and neonatal pancreases were then analysed for their morphometry.
resultsIn vitro metformin treatment led to an increase in the proliferation and number of pancreatic duodenal homeobox 1-positive (PDX1(+)) progenitors. These results were reproduced by in vitro culture of embryonic pancreas rudiments with AICAR, suggesting that AMPK activation was involved. Similarly, metformin administration to pregnant dams induced an increase in both PDX1(+) and neurogenin 3-positive progenitors in the embryonic pancreas at E14.0 and these changes resulted in an increased beta cell fraction in neonates. CONCLUSIONS/
interpretationThese results indicate that exposure to metformin during gestation modulates the early steps of beta cell development (prior to E14.0) towards an increase in the number of pancreatic and endocrine progenitors. These changes ultimately result in a higher beta cell fraction at birth. These findings are of clinical importance given that metformin is currently used for the treatment of gestational diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.