Increased susceptibility to streptozotocin and impeded regeneration capacity of beta-cells in adult offspring of malnourished rats
| Autor: | Claude Remacle, Thomas Bouckenooghe, Brigitte Reusens, Giorgia Sisino, Kevin Goosse, Sandra Aurientis |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Aging Physiology Offspring medicine.medical_treatment Drug Resistance Biology Fetal Nutrition Disorders Streptozocin Low-protein diet Pregnancy Diabetes mellitus Internal medicine Insulin-Secreting Cells Protein Deficiency medicine Weaning Endocrine system Animals Regeneration Rats Wistar Cells Cultured Cell Proliferation Fetus Streptozotocin medicine.disease Rats Endocrinology Prenatal Exposure Delayed Effects Gestation Female medicine.drug |
| Zdroj: | Acta physiologica (Oxford, England). 210(1) |
| ISSN: | 1748-1716 |
| Popis: | Background: Epidemiological studies related poor maternal nutrition and subsequent growth retardation in the progeny to the development of diabetes later in life. Low-protein diet during gestation altered the beta-cell development of the rat progeny by decreasing beta-cell proliferation and increasing their sensitivity to nitric oxide and cytokines in the foetus. This disturbed maternal environment had long-lasting consequences because the higher beta-cell vulnerability was maintained at adulthood. Aim: The aim of this study was to determine whether early malnutrition influences the vulnerability and the regeneration capacity of beta-cells after streptozotocin (STZ) damage at adulthood. Methods: Gestating rats were fed either a control or a low-protein diet until weaning. Adult female offspring received injections of Freund's adjuvant weekly for 5 weeks followed 24 h later by STZ. Half of the cohort was killed at d34, whereas the other half was maintained until d48 to analyse the regeneration capacity of the beta-cells. Results: Although control and low-protein rats had equivalent pancreatic insulin content and beta-cell volume density at d34, hyperglycaemia appeared earlier and was more dramatic in low-protein rats than in control rats. STZ treatment increased beta-cell proliferation similarly in both groups. At d48, apoptotic rate was higher in the low-protein group. Regeneration appeared in control, but not in the low-protein rats, where beta-cell aggregates/surface area and Reg1-positive area were decreased compared to control. Conclusion: Maternal malnutrition programmes a more vulnerable endocrine pancreas in the progeny which is unable to regenerate after injury, therefore predisposing it to develop glucose intolerance and diabetes later in life. |
| Databáze: | OpenAIRE |
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