Implication of nitric oxide in the increased islet-cells vulnerability of adult progeny from protein-restricted mothers and its prevention by taurine.
An increased vulnerability of adult beta-cells seems to be programmed in early life as adult islets from the progeny of dams fed a low-protein diet exhibited an increased apoptotic rate after cytokine stimulation. This was prevented by maternal taurine supplementation. Here, we investigated the mechanisms implicated in such an increased vulnerability and how taurine exerts its protective role. Throughout gestation and lactation, Wistar rats were fed a 20% (control (C group)) or an isocaloric 8% protein diet (recovery (R group)) supplemented or not with taurine (control+taurine and recovery+taurine groups respectively). Offspring received a 20% protein diet after weaning. Islets from 3-month-old females were isolated and cultured for 48 h before being incubated with or without cytokines for 24 h. In unstimulated islets, apoptotic rate and NO(.) secretion were higher in R than in C. Both GADD153 mRNA and protein were increased, whereas mRNA of mitochondrial gene ATPase6 was downregulated in R group compared with C. In the RT group, taurine prevented apoptosis and restored a normal NO(.) production in GADD153 as well as ATPase6 mRNA expression. After cytokines-induction, apoptosis and NO(.) secretion were still increased in R compared with C but both parameters were normalized in the RT group. In conclusion, a maternal low-protein diet programmes a different pattern of gene expression in islet-cells of adult progeny. Higher NO(.) production by these islets could be an important factor in the subsequent cell death. The prevention of these events by maternal taurine supplementation emphasizes the importance of taurine during endocrine pancreas development.
Goosse
K
K
Laboratory of Cell Biology, Université Catholique de Louvain, Place Croix du Sud 5, 1348 Louvain-La-Neuve, Belgium.
Bouckenooghe
T
T
Balteau
M
M
Reusens
B
B
Remacle
C
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018753:Diet, Protein-Restricted; D005260:Female; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage*
D013654:Taurine; D009569:Nitric Oxide