Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet
Open accessAbstract
Aims/hypothesis Adverse events during intra-uterine life may programme organ growth and favour disease later in life. In animals, protein or energy restriction during gestation alters the development of the endocrine pancreas, even though the duration of malnutrition is different. Here, we evaluate the specific effects of both diets during different periods of gestation and the mechanisms underlying the decreased beta cell mass.Methods Pregnant Wistar rats were fed either a low-protein or a low-energy diet during the last week of gestation or throughout gestation. Fetuses and their pancreases were analysed at days 15 and 21 of gestation.Results The low-energy diet reduced the beta cell mass from 21-day-old fetuses by 33 or 56% when administered during the last week or throughout gestation, respectively. Fetal corticosterone levels were increased. At 15 days of fetal age, the number of cells producing neurogenin 3 (NEUROG3) or pancreatic and duodenal homeobox gene 1 (PDX-1) was reduced. Neither islet vascularisation nor beta cell proliferation was affected. The low-protein diet, in contrast, was more efficient in decreasing the fetal beta cell mass when given during the last week of gestation (-53%) rather than throughout gestation (-33%). Beta cell proliferation was decreased by 50% by the low-protein diet, independently of its duration, and islet vascularisation was reduced. This diet did not affect NEUROG3- or PDX-1-positive cell numbers.Conclusion/interpretation Although both diets reduced the fetal beta cell mass, the cellular mechanisms and the sensitivity windows were different. Early alteration of neogenesis due to elevated corticosterone levels is likely to be responsible for the decreased beta cell mass in low-energy fetuses, whereas impaired beta cell proliferation and islet vascularisation at later stages are implicated in low-protein fetuses.
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A growth-restricted fetus has fewer insulin-producing beta cells and reduced vascularization in the pancreas, and compromised structure and maturation of the brain, lungs, and liver.
“In addition, the pancreas has fewer insulin-producing beta cells and reduced vascularization (159, 340, 473), and the structure and maturation of the brain (142), lungs (358, 359, 424, 460) and liver (209, 474) are compromised.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [159]
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- Authors
- Dumortier, O., Blondeau, B., Duvillié, B., Reusens, B., Bréant, B., & Remacle, C.
- Affiliations
- UCLouvain (BE)
- Inserm (FR)
- Hôpital Necker-Enfants Malades (FR)
- Corresponding author
- Remacle, C.
- Venue
- Diabetologia
- Published
- 2007-09-19
- Volume
- 50
- Issue
- 12
- Pages
- 2495-2503
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2086663036
- Cited by
- 124
- References
- 45
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 8 · 2012: 10
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Funders
- Université de Lille
- European Commission
- Institut National de la Santé et de la Recherche Médicale
- Fonds De La Recherche Scientifique - FNRS
- Parthenon Trust
- Université Lille 1 - Sciences et Technologies
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- maternal low-protein diet, corticosterone, neurogenin 3, PDX1, beta-cell proliferation, developmental programming
- MeSH terms
- Animals, Blood Glucose, Energy Intake, Corticosterone, Diet, Reducing, Female, Gestational Age, Insulin, Islets of Langerhans, Maternal-Fetal Exchange, Organ Size, Pregnancy, Protein-Energy Malnutrition, Time Factors, Signal Transduction, Rats, Wistar, Diet, Protein-Restricted, Fetal Weight, Caloric Restriction, Pancreas, Exocrine, Insulin-Secreting Cells, Rats
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