Early low protein diet increases foetal and adult islet sensitivity to cytokines : protective role of taurine
(2003)
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- Epidemiological studies have suggested that malnutrition during development, which leads to offspring growth retardation, might be at the origin of syndrome X later in life. This syndrome includes hypertension, obesity and the propensity to type-2 diabetes. In animal model, it was demonstrated in our laboratory that early protein deficiency (8%; LP vs. 20%; C) alters foetal pancreas development. Indeed, the mass of endocrine pancreas and its vascularisation were reduced. Islet cells featured a higher apoptotic rate, this has prompted us to emit the hypothesis of possible early "programming" of susceptibility to molecules involved in type-1 diabetes following protein deficiency in early life. Therefore, we first investigated the effect of early LP diet on the sensitivity of foetal islet cells to NO. and IL1-â. We found that foetal islets from rats fed on LP diet during gestation were more sensitive to these toxic molecules than control islets. Thereafter, we verified the long-lasting effect of LP diet on islet cells sensitivity to cytokines, when this diet was kept during gestation and lactation (recuperated group, R). Adult islets of the R group remained more sensitive to cytokines despite refeeding a normal diet after weaning. Thus, a permanent alteration in susceptibility of beta cell appeared programmed in foetal life. LP diet has been reported to decrease the level of plasma taurine in dams and their foetuses. Since this amino acid is considered to feature antioxidant properties, we verified the effect of taurine either added in vitro or in vivo to the drinking water (2.5%) of the mother on the sensitivity of foetal and adult islets to cytokines. When taurine was added to the culture medium of foetal and adult islets it provided an important protective effect against cytokines-induced apoptosis. In vivo, it lowered the sensitivity of foetal islets of control group to IL1-â but not to NO. donor. In islets of LP group, the cytotoxic response to IL1-â was suppressed and that to NO. donor was decreased. Taurine supplementation in vivo during early life decreased the susceptibility of adult islets of the R group to cytokines. Whereas, it increased the sensitivity of the controls. On the other hand, when an oral glucose tolerance test (OGTT) was performed at this age, the administration of taurine in early life restored the insulinaemia in R group, while it remained blunted with the absence of treatment by the amino acid. Together these findings emphasize that a normal level of taurine during early life is important for an appropriate function and resistance to aggression in the endocrine pancreas. Some mechanisms by which taurine could exert its protection on beta cell were also investigated in this work. We showed first that the beneficial effect of taurine must be attributed to its sulphonic group, since analogous amino acids, like methionine and b-alanine, were less effective. Second, in an acellular system, taurine appears to react with ONOO- but not with NO.. Finally, in a cellular system, we used rat insulonoma cell line (RINm5F), which was also protected by taurine treatment towards cytokines injury. In this system, we found that the anti-apoptotic effect of taurine does not appear to be related to changes in HSP70 expression, but a decrease in NO. production could be involved. In conclusion, our study demonstrated that LP diet during development increased the sensitivity of beta cell to cytokines suggesting a possible link between foetal "programming" and type-1 diabetes later in life. Moreover, the beneficial effect of taurine was demonstrated in foetal and adult islet cells underlining the important role of normal taurine level during endocrine pancreas development.
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Merezak, S. (2003). Early low protein diet increases foetal and adult islet sensitivity to cytokines : protective role of taurine. https://hdl.handle.net/2078.5/97878