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Islet function in offspring of mothers on low-protein diet during gestation
S Dahri1, A Snoeck, B Reusens-Billen
1Laboratory of Cell Biology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Insights
Maternal low-protein diets impair fetal pancreatic development, leading to lasting insulin secretion defects in offspring. Nutritional interventions after birth do not fully correct these developmental issues.
Area of Science:
- Endocrinology
- Developmental Biology
- Nutritional Science
Background:
- Maternal nutrition significantly influences fetal development.
- A low-protein diet during pregnancy has been shown to affect offspring endocrine pancreas structure and function.
Purpose of the Study:
- To investigate the functional consequences of in utero exposure to a low-protein diet on fetal islet insulin secretion.
- To determine if dietary interventions postnatally can reverse the functional deficits in insulin secretion.
Main Methods:
- Offspring from dams fed a low-protein (8%) or control (20%) diet during gestation were studied.
- Fetal pancreatic islets were isolated and stimulated in vitro with amino acids (arginine, leucine).
- Insulin secretion, glucose tolerance, and fasting insulin/glucose levels were assessed at various ages.
Main Results:
- Low-protein diet during pregnancy reduced fetal islet cell proliferation, size, vascularization, and insulin content.
- Fetal islets exposed to the low-protein diet showed impaired insulin secretion in response to amino acid stimulation.
- Offspring on a low-protein diet throughout life exhibited low fasting insulin levels and impaired glucose tolerance, with a blunted insulin response.
- A normal diet from birth did not restore normal insulin response, indicating permanent damage.
Conclusions:
- A low-protein diet during pregnancy induces lasting functional damage to the fetal endocrine pancreas.
- Adequate maternal nutrition is crucial for normal development of the endocrine pancreas and prevention of long-term metabolic dysfunction.
- Dietary interventions postnatally cannot fully compensate for prenatal nutritional insults affecting pancreatic development.
Abstract:
A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.