Low-Protein Diet Late in Fetal Development Affects mTOR Signaling
Botezatu, Nathalie M.
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Type 2 diabetes is characterized by inadequate pancreatic beta-cell function and insulin resistance. Insufficient nutrition during critical time windows of fetal development may predispose offspring to type 2 diabetes. Previous studies with in utero protein restriction models (IUPR) showed that offspring of low-protein fed mothers were permanently growth restricted despite being weaned on a normal diet. This study focused on the effects of the LP 12.5 model, in which a maternal low-protein diet was administered during the last week of gestation. Western-blot analysis was performed on key factors relevant to the mTOR pathway, a pathway crucial to pancreatic beta-cell development. Protein levels of mTOR and phosphorylated Akt sites (Ser473) and (Thr308) showed an increasing trend in LP12.5 offspring, suggesting a compensatory mechanism due to nutrient deprivation. Protein levels of phosphorylated S6 sites (Ser235) and (Ser240) showed decreasing trends in comparison to control mice, which may suggest a direct relationship of nutrient deprivation on S6 protein. The expression of Olinked GlcNAc transferase (OGT), a highly expressed protein in beta-cells involved in protein post-translation modification, was also analyzed. There were trends of increase in OGT protein levels in LP12.5 females and decrease in males compared to controls. Though the acquired data approached, but did not reach, statistical significance, further study with larger sample sizes could confirm the observed trends, providing a better understanding of the affects of nutrient deprivation during fetal pancreatic beta-cell development and its relation to type 2 diabetes susceptibility. A better understanding of the mTOR pathway and related factors could lead to the therapeutic development of treatments that may enhance beta-cell function in instances of nutrient deprivation.