Beta cell vulnerability and regeneration in the adult progeny of low protein-fed mothers : prevention by taurine
(2008)
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- Abstract
- Epidemiological studies related poor maternal nutrition and subsequent growth retardation in the progeny to the development of diabetes later in life. In the laboratory, a rat model was developed where maternal low protein diet [8% protein isocaloric diet vs 20% protein diet in controls (C)] led to offspring with low birth weight and with altered endocrine pancreas development. Moreover, islets of this progeny exhibited higher level of apoptosis when incubated with nitric oxide donor or with cytokines. These effects persisted until adulthood even if the 20% protein diet was given after weaning [Recovery (R) group, fed 8% protein diet during gestation and lactation followed by 20% protein diet until adulthood]. On the other hand, maternal low protein diet reduced the plasma level of taurine in mothers and foetuses. Supplementation with this amino acid restored the vulnerability of islet-cells in both foetuses and adults. This study was designed to understand why maternal low protein-diet led to increased vulnerability of the adult islets and how taurine could exert its protective role. In a first set of experiments, we demonstrated that inadequate feeding during development of the foetus and the neonate permanently modifies the expression of genes involved in ER stress and mitochondrial metabolism in islets of the adult progeny. Higher nitric oxide production may be one the key player in the subsequent cell death. Early taurine supplementation to these rats normalized apoptosis in the adult islets by restoring the expression of all the modified genes. We then developed a model of beta cell destruction in rat mediated by the injections of multiple low doses of streptozotocin (STZ) with the purpose to study the response of islets toward toxic agent in vivo. We observed that the increase in glycaemia was higher in R rats. Moreover, compared to C animals, R rats did not recover from beta cell destruction. Early taurine supplementation prevented from hyperglycaemia but was inefficient to improve beta cell regeneration. Thus, we showed in this study that maternal protein-deficiency increased islet-cell vulnerability and impaired STZ-induced beta cell regeneration in the adult offspring. Maternal taurine supplementation to low protein diet rescued beta cell apoptosis but provided limited protection after STZ destruction.
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Goosse, K. (2008). Beta cell vulnerability and regeneration in the adult progeny of low protein-fed mothers : prevention by taurine. https://hdl.handle.net/2078.5/124081