Glycine supplementation during six months does not alter insulin, glucose or triglyceride plasma levels in healthy rats.

Nowadays, glycine is used in nutritional supplements and to attenuate chronic complications of diabetes and obesity; however, its use has side effects as insulin resistance. Our aim was to evaluate the effect of chronic glycine supplementation on insulin, glucose and triglyceride levels in healthy Wistar rats. Groups were: Control (C), that received sterilized water only, glycine (GG), that received 1% glycine and taurine (TG), that received 0.5% taurine during 6 months (n = 10). Our results showed no differences in plasma insulin levels after six months of supplementation (C: 13.22 ± 2.0; GG: 11.4 ± 2.0; TG: 11.13 ± 2.0 ng/ml; p = 0.64). Likewise, neither glucose plasma concentration (C: 99.9 ± 3.9 mg/dl; GG: 104.3 ± 4.3 mg/dl; TG: 104.5 ± 4.8 mg/dl) (p = 0.88) nor triglyceride levels (C: 58.4 ± 5.6 mg/dl; GG: 46.9 ± 2.3 mg/dl; TG: 50.68 ± 3.3 mg/dl), showed differences after six months supplementation (p = 0.22). Furthermore, the analysis of glycine (C: 80 ± 24.6; GG: 83.9 ± 25.9; TG: 90.7 ± 13.5 nmol/ml) (p = 0.19) and taurine (C: 169 ± 15.17; GG: 148.7 ± 23.9; TG: 165.8 ± 22.5 nmol/ml) (p = 0.4) in the plasma of animals with supplementation showed no significant changes. Additionally, general urine tests and histological analysis of liver or kidneys showed no alterations. In conclusion, chronic supplementation with 1% glycine did not have any significant detrimental side effects in our model. However, more studies are still necessary to evaluate the effect of 1% glycine supplementation in humans.

An association between glycine and insulin levels is observed in patients with pulmonary tuberculosis and type 2 diabetes.

BACKGROUND & AIMS: Adequate nutrition from which amino acids are part gives us protection against infectious or metabolic diseases. In particular, glycine has immunomodulatory properties and is a secretagogue of insulin. However, its absorption rate or plasma levels are impaired in bacterial infection or high glucose levels. The aim of this study was to evaluate the association between glycine and insulin plasma levels in patients with pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (DM2). METHODS: Plasma levels of insulin and glycine were determined in four groups: 1) patients with PTB; 2) patients with PTB-DM2; 3) household contacts with DM2 (C-DM2), and 4) healthy household contacts (H-C). Likewise, we analyzed the plasma levels of glucose, serine, arginine, lysine, taurine, and glutamic acid. RESULTS: We observed significant differences in the glycine levels between PTB and PTB-DM2 vs C-DM2 and H-C groups (P < 0.05). We observed also important differences in insulin and glucose levels after comparisons between PTB, PTB-DM2, and C-DM2 vs. H-C groups (P < 0.05). A correlation between glycine and insulin levels in the PTB (r = 0.326) and PTB-DM2 (r = 0.318) groups was found. CONCLUSION: Our results showed a significant association between glycine and insulin plasma levels in patients with PTB and PTB-DM2, which suggests that the determination of glycine levels could be used as a reference test to evaluate both pathologic conditions. An additional support to the above is that significant changes in the glucose levels in these groups were observed, too.

Incubation with DNase I inhibits tumor cell proliferation.

BACKGROUND: Deoxyribonuclease I (DNase-I) plays an important role in the elimination of damaged-, aging- or cancer cells. Various authors suggest that programmed cell death (PCD) is attenuated in cancer cells due to a reduced activity of DNase-I. MATERIAL AND METHODS: In this work, we evaluated cell viability (violet crystal stain), cell proliferation (tritiated thymidine) and DNA degradation of tumoral cells (Calu-1, SK-MES-1, HeLa, HEp-2, L-929) incubated with different concentrations of DNase I. PBMN cells and human fetal fibroblasts served as controls. RESULTS: Our results showed a >90% decrease in the viability of HeLa and HEp-2 cells, and >50%<90% decline in Calu-1, SK-MES-1 and L-929 cell viability, incubated with 9 mg/ml of DNase-I in comparison with control cells (p<0.05). The incorporation of [3H]thymidine showed a 50% decrease in tumoral cells. Control cells showed no significant differences. Tumor cell DNA degradation was observed after nuclease treatment, however the typical DNA ladder, characteristic of the apoptotic cell, was not observed. The morphology of some DNAse-I treated tumor cells suggested autoschizis CONCLUSION: Our results suggest that the use of a DNA nuclease might have some benefits in the treatment of cancer since it inhibits cell growth, probably by inducing autoschizis.

Association between IL-15 and insulin plasmatic concentrations in patients with pulmonary tuberculosis and type 2 diabetes.

IL-15 is part of the immune response in pulmonary tuberculosis (PTB) but amazingly, it may also induce physiological effects similar to those of insulin. We evaluated the IL-15 and insulin plasmatic levels in adults with PTB and with or without type 2 diabetes mellitus (DM2), who received previous antituberculosis therapy for at least 2 months. We analyzed the concentrations of glucose, glycated hemoglobin, insulin, as well as levels of IL-15, IL-2, IFN-γ, and TNF-α in patients with PTB, patients with PTB-DM2, household contacts with DM2 (C-DM2), and healthy household contacts (H-C). Our results showed unexpected high levels of glucose, insulin, and IL-15 in the PTB and C-DM2 groups. In comparison, low levels of these same indicators were observed in the PTB-DM2 and H-C groups. Interestingly, our analysis showed a positive correlation of IL-15 with insulin in the PTB group (r = 0.73) and in the C-DM2 group (r = 0.66). In comparison, a weak correlation between IL-15 and insulin was observed in the PTB-DM group (r = 0.10) and in the H-C group (ρ = 0.26). Our results suggest an association between IL-15 and insulin levels in the patient with PTB. Intriguingly, this association was weaker in the patient with PTB-DM2.

Effect of amyloid-Β (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein.

Aggregation of the amyloid beta (Aß) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1. Weight, glycated hemoglobin, glucose, and insulin were determined. Male Wistar rats were divided in groups (N=20): a) control, b) treated only with the Aß25-35 peptide, c) treated with Aß25-35 and STZ, and d) treated only with STZ. Results showed statistically significant differences in the mean weight, glucose levels, insulin concentration, and HbA1c percentage, between C- and D-treated groups and not STZ-treated A and B (P<0.05). Interestingly, our results showed diminution of O-GlcNAcylation and increase in P-tau-Ser-396 in the hippocampal area of the Aß25-35- and STZ-treated groups; moreover, enhanced expression of GSK3beta was observed in this last group. Our results suggest that hyperinsulinemia-Aß25-35-hyperglycemia is relevant for the down regulation of O-GlcNAcylation and up-regulation of the glycogen synthase kinase-3 beta (GSK3beta), favoring Aß25-35-induced neurotoxicity in the brain of rats.

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats.

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.

Effect of glycine in streptozotocin-induced diabetic rats.

Inadequate utilization of glucose in diabetes mellitus favors diverse metabolic alterations that play a relevant role in the physio-pathology of chronic complications of this disease. Streptozotocin-induced diabetic rats were treated daily with glycine (130 mM as optimal concentration) or taurine (40 mM) for six months. Groups of diabetic rats without treatment were used as controls. Glucose, total cholesterol, triacylglycerol, and glycated hemoglobin were determined periodically after inducing diabetes. Rats were killed after 6 months of treatment and histological analyses were performed. Diabetic groups that received glycine or taurine showed significant lower concentrations of glucose, total cholesterol, triacylglycerol, and glycated hemoglobin than diabetic control rats (P<0.05) after 6 months treatment. Histological analyses of diabetic rats showed pancreatic atrophy and necrosis, vacuolization, decrease of beta cells, and diffuse glomerulosclerosis. Diabetic rats treated with glycine or taurine showed less enlargement of the glomerular basal membrane than control diabetic rats. Our results suggest that glycine and taurine reduced the alterations induced by hyperglycemia in streptozotocin-induced diabetic rats probably due to inhibition of oxidative processes.