The hippocampus were isolated and we isolated the synaptosome as follows

sent study. Safety of glutamine supplementation of enteral or parenteral nutrition was widely studied in critically-ill patients where Lglutamine is used to maintain intestinal integrity, ONO4059 improve nitrogen balance, prevent infections, decrease oxidative stress and improve survival. Glutamine supplementation in critically-ill patients resulted in conflicting findings, including decreased, increased or no effect on complications and mortality rates. Type 2 diabetes has been associated with decreases in circulating glutamine previously but, in this well-controlled diabetic cohort plasma glutamine concentrations were within the reference range. Glutamine supplementation at levels of 130 g/d are safe for several hours post ingestion in physically active healthy populations and type 2 diabetes patients. However, safety data of prolonged glutamine intake in non-critically-ill patients are scarce. Bold values represent P,0.05. Normal probability plots of the P-values versus PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1968231 their rank were examined to determine statistical significance. Relationships that were found to be non-linear were indicative of statistically significant results. The data below P of 0.05 were in the non-linear regions. doi:10.1371/journal.pone.0113366.t002 days of glutamine or casein supplementation in healthy, predominantly sedentary, middle age and elderly individuals in dosages slightly higher than those administered here. Unlike the present study, serum creatinine concentrations increased and eGFR decreased with glutamine or casein, maybe due to the higher protein intake. Similarly to the present study however, blood urea concentrations increased, reflecting the increased dietary nitrogen intake. Interestingly, blood cells, Hb, Hct, total protein and albumin concentrations were all decreased with glutamine in the present study. The decreases in red blood cells without changes in MCV, MCH and MCHC and the general decreases in circulating macromolecules suggest intravascular fluid volume expansion, an effect previously documented in piglets with parenteral glutamine supplementation. Notably, body weight and plasma electrolytes were unchanged in PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19683642 the present study, consistent with minor changes in plasma volume or changes in fluid distribution. The mechanisms involved in extracellular fluid volume expansion with glutamine are unclear, but have been suggested to involve increased glomerular sodium reabsorption , which with prolonged glutamine ingestion may alter electrolyte concentrations and acid-base regulation. Furthermore, modest decreases in Hb and Hct were also noted previously with high dose glutamine or casein supplementation for 14 days in healthy individuals, suggesting that these effects are not limited to glutamine or type 2 diabetes patients. In any case, further study is required to determine the mechanisms involved in the effect of glutamine on plasma volume expansion. This is the first study to evaluate the effect of daily glutamine supplementation for a period of weeks on glycemic control and safety in type 2 diabetes patients. There are several strengths to the study, including the sitagliptin versus placebo crossover design that enabled investigation of possible interaction between glutamine and DPP-4 inhibition. Furthermore, the homogeneity of the cohort in terms of age, disease duration and background diabetes treatment increased the power to detect the effects of the treatment on the endpoints. The main limitation of the study is the lack of sitaglipt