Influence de l'environnement intra-utérin sur le développement du pancréas endocrine
(2008)
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- Authors
- Supervisors
- Remacle, Claude
- Abstract
- Epidemiological studies have revealed the strong relationships between poor foetal growth and subsequent development of the metabolic syndrome, including insulin resistance and type II diabetes. This led to the hypothesis that some programming of these pathologies originates in early life. To elucidate the mechanisms underlying such programming, animal models of intrauterine growth retardation induced by maternal malnutrition have been designed. Whatever the type of foetal malnutrition, malnourished pups are born with a defect in their beta-cell population that will never completely recover. However, not only the nature of the nutrient deficit, but also the duration of exposure differed. It is conceivable that the different time-windows would perturb the endocrine pancreas in different ways since its development follows a very precise time-schedule of regulation. First, we evaluated the specific effects of a low protein and a low calorie diets during different periods of gestation and the mechanisms underlying the decreased beta cell mass. Although both diets reduced the fetal beta cell mass, the cellular mechanisms and the sensitivity windows were different. Early alteration of neogenesis is likely to be responsible for the decreased beta cell mass in low calorie foetuses, whereas impaired beta cell proliferation and islet vascularisation at later stages are implicated in low protein foetuses. In the second set of experiment we investigated whether glucocorticoids (GCs) may are implicated in pancreatic alteration due to 8 malnutrition and if the time window during which GCs are administered will differently affect the fetal pancreas. The developing pancreas is sensitive to an excess of GCs which reduces the beta- and alpha-cell mass by different mechanisms according the stage of development. However they do not explain all pancreatic alterations observed with our different malnutrition models. Accumulating evidence suggests that endothelial cells may participate in the development of the endocrine pancreas. However, the cross-talk between endothelial cells and pancreatic beta-cells it still poorly understood. In the third part of this work, we aimed to obtain, purify and propagate rat islet endothelial cells. We have developed a technique that may be used as a rat islet angiogenesis assay. Using such system, it is possible to study mechanisms of the angiogenic process under standardized experimental conditions.
- Affiliations
Citations
Dumortier, O. (2008). Influence de l’environnement intra-utérin sur le développement du pancréas endocrine. https://hdl.handle.net/2078.5/97574