Vascular endothelial function is improved by oral glycine treatment in aged rats.

Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 ß was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase activity and mRNA expression in muscle is related to glucosamine-induced insulin resistance.

Glucosamine (GlcN)-induced insulin resistance is associated with an increase in O-linked-N-acetylglucosaminylated modified proteins (O-GlcNAcylated proteins). The role played by O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase (O-GlcNAcase), which removes O-N-acetyl-glucosamine residues from O-GlcNAcylated proteins, has not yet been demonstrated. We investigated whether GlcN-induced whole-body insulin resistance is related to tissue O-GlcNAcase activity and mRNA expression. GlcN (30 mumol/kg/min) or physiological saline (control) was intravenously infused into Sprague-Dawley rats for 2 h. After GlcN treatment, rats were subjected to the following: intravenous glucose tolerance test, insulin tolerance test or removal of the liver, muscle and pancreas. GlcN was found to provoke hyperglycemia compared to control (8.6 +/- 0.41 vs. 4.82 +/- 0.17 mM, p < 0.001). The insulin resistance index (HOMA-IR) increased (15.76 +/- 1.47 vs. 10.14 +/- 1.41, p < 0.001) and the beta-cell function index (HOMA-beta) diminished (182.69 +/- 22.37 vs. 592.01 +/- 103, p < 0.001). Liver glucose concentration was higher in the GlcN group than in the control group (0.37 +/- 0.04 vs. 0.24 +/- 0.038 mmol/g dry weight, p < 0.001). Insulin release index (insulin/glucose) was less in the GlcN group than in the control (2.2 +/- 0.1 vs. 8 +/- 0.8 at 120 min, p < 0.001). In the GlcN group, muscle O-GlcNAcase activity diminished (0.28 +/- 0.019 vs. 0.36 +/- 0.018 nmol of p-nitrophenyl/mg protein/min, p < 0.001), and K(m) increased (1.51 +/- 0.11 vs. 1.12 +/- 0.1 mM, p < 0.001) compared to the control. In the GlcN group, O-GlcNAcase activity/mRNA expression was altered (0.6 +/- 0.07 vs. 1 +/- 0.09 of control, p < 0.05). In conclusion, O-GlcNAcase activity is posttranslationally inhibited during GlcN-induced insulin resistance.

Waist perimeter cutoff points and prediction of metabolic syndrome risk. A study in a Mexican population.

BACKGROUND: Association between metabolic syndrome (MS) risk factors was analyzed to establish optimum waist perimeter (WP) cutoff points for a Latin American cluster. METHODS: There were 1036 clinically healthy Mexican subjects without a history of CVD. Their full medical history and anthropometric and biochemical parameters were analyzed. Diagnosis of MS was classified by both the International Diabetes Federation (IDF) and the American Heart Association (AHA-NHLBI) definitions. The optimum WP cutoff point was defined through one-way ANOVA, homogeneity and chi(2) test of dependency, and receiver operator characteristic analysis (ROC). RESULTS: WP cutoff points suggested by the IDF (> or =90 cm in men, > or =80 cm in women) and AHA-NHLBI (> or =102 cm in men, > or =88 cm in women) showed a weak association with the other MS risk factors. By using the cutoff point of > or =98 cm for men and > or =84 cm for women, we obtained maximum sensitivity and specificity values by ROC analysis. These cutoff points defined as the Mexican Waist Perimeter Proposal (MxWPP) significantly change the prevalence of MS in contrast with the IDF and AHA-NHLBI. CONCLUSIONS: Applying the MxWPP new criteria enhances the capability to more accurately detect subjects with MS risk in an apparent healthy Latin American cluster.

Effect of an intensive metabolic control lifestyle intervention in type-2 diabetes patients.

OBJECTIVE: To evaluate the effectiveness of an intensive lifestyle intervention on metabolic control in patients with type 2 diabetes. METHODS: 199 patients recently diagnosed with type 2 diabetes, with lack of metabolic control and overweight/obesity, were randomly assigned to intensive lifestyle intervention or collaborative educational program alone, with 6 months of follow-up. Intervention included 150min of physical activity a week to reduce body weight by 7%. Both groups received 16 sessions on behavior modification over the course of the 6 months. Measurements were taken at baseline, 3 and 6 months. Results were analyzed and compared. RESULTS: Significant weight loss was achieved by both groups, with greater loss in the intervention group. Those with lower baseline A1c appeared to benefit more from the educational program than intensive intervention over time. CONCLUSIONS: Both interventions produced positive if modest changes in metabolic control. These results suggest that, for weight loss and control of A1c, an intensive intervention may be more effective. PRACTICE IMPLICATIONS: The current study demonstrates the value of a systematic application of behavior modification and self-care techniques in the treatment of type 2 diabetes. It demonstrates the importance of intensive, all-inclusive treatment, and of attention to individual concerns.

Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight.

OBJECTIVE: The aim of this study was to describe the agreement between impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in children with excess body weight using the original and the revised definitions of IFG. RESEARCH DESIGN AND METHODS: Obese and overweight children aged 4-17 years were included (n = 533). Anthropometric parameters and biochemical tests (fasting and 2-h glucose tests after an oral glucose load [1.75 g/kg]) were performed. Case subjects with a fasting plasma glucose >/=126 mg/dl were excluded. The diagnostic parameters of the original and the revised definitions of IFG for detecting IGT were estimated. The analysis of agreement between these categories was made using the kappa test. RESULTS: The prevalence of IFG increased from 6.2 to 13.3% using the new criteria. The prevalence of IFG became closer to the prevalence of IGT (14.8%). The revised criteria increased the sensitivity from 26.6 to 36.7%. However, the new IFG definition was not useful for identifying IGT cases. Of the 71 case subjects with IFG, only 29 (40.8%) had IGT. In addition, 50 case subjects with IGT (9.4%) and 13 with diabetes (2.4%) had a fasting glycemia <100 mg/dl. A poor agreement was found between the 2003 IFG definition and abnormal 2-h postchallenge plasma glucose (kappa = 0.359). The proportion of false-positive cases increased (36.3-59.1%) under the new definition. CONCLUSIONS: The new definition modestly increases the sensitivity of IFG for detecting IGT in children with excess body weight. Despite this, more than one-half of these cases are not detected. In addition, the false-positive rate was increased by 61%.

Degradation of pro-insulin-receptor proteins by proteasomes.

BACKGROUND: Type-2 diabetes is characterized by hyperinsulinemia, peripheral insulin resistance, and diminished tyrosine phosphorylation activity. It has been recently shown that proteasomes are implicated in the degradation of the insulin receptor substrate-1 (IRS-1) but not in that of the insulin receptor (IR). However, it is unknown whether proteasomes are involved in pro-IR degradation. METHODS: We used CHO-IR and the 3T3-L1 cells treated with insulin at different concentrations and compared the proteasome activity of IRS-1, IR, and pro-IR degradation either in presence or in absence of lactacystin. RESULTS: A total of 100 nM of insulin allowed degradation of IRS-1 after 6 h of incubation. At 1,000 nM of insulin, pro-IR degradation began at 1 h of incubation, similar to IRS-1 degradation. Surprisingly, at a higher concentration (10 microM) of insulin, a drastic decrease of proteins was observed from the first minute of incubation. This activity was blocked by lactacystin, a specific proteasome inhibitor. CONCLUSIONS: According to these results, we propose that pro-IR is degraded by proteasomes.

Type 2 diabetes mellitus in children--an increasing health problem in Mexico.

The incidence of type 2 diabetes mellitus (DM2) in children has increased worldwide and is commonly associated with overweight. Forty-four children with DM2 were studied by clinical histories, anthropometric measurements, and biochemical analysis. Homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were determined to evaluate insulin resistance. Only five patients presented normal body mass index (BMI); the remainder were overweight, and 76% had acanthosis nigricans. Laboratory results yielded hyperglycemia, elevated glycosylated hemoglobin, insulin and C-peptide. Elevated HOMA-IR and decreased QUICKI values suggest insulin resistance. No significant difference was found between sexes, although overweight in girls had more influence over blood pressure and lipid levels (p <0.05). Time from diagnosis and HOMA-IR yielded relevant values (p = 0.010). Laboratory results, QUICKI, and HOMA-IR values suggested that these patients present DM2 and decreased insulin sensitivity. We recommend prevention of overweight and sedentary life-style.

Glycine suppresses TNF-α-induced activation of NF-κB in differentiated 3T3-L1 adipocytes.

Glycine strongly reduces the serum levels of pro-inflammatory cytokines and increases the levels of anti-inflammatory cytokines. Recently, glycine has been shown to decrease the expression and secretion of pro-inflammatory adipokines in monosodium glutamate-induced obese (MSG/Ob) mice. It has been postulated that these effects may be explained by a reduction in nuclear factor kappa B (NF-κB) activation. NF-κB is a transcription factor, which is crucial to the inflammatory response. Hasegawa et al. (2011 and 2012) recently reported a glycine-dependent reduction in NF-κB levels. Here, we have investigated the role of glycine in the regulation of NF-κB in differentiated 3T3-L1 adipocytes. The results revealed that pretreatment with glycine interfered with the activation of NF-κB, which has been shown to be stimulated by tumor necrosis factor-alpha (TNF-α). Glycine alone stimulated NF-κB activation in an unusual way such that the inhibitor κB-ß (IκB-ß) degradation was more significant than that of the inhibitor κB-α (IκB-α) and led to NF-κB complexes comprised of p50 and p65 subunits; IκB-ε degradation did not affect by glycine. These findings suggest that glycine could be used as an alternative treatment for chronic inflammation, which is a hallmark of obesity and other comorbidities, and is characterized by an elevated production of pro-inflammatory cytokines.

Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors.

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8-22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7-8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

Las infecciones prevenibles por vacunacion / Infections preventable through vaccination

En este articulo se presenta una revisión de la evolución de la práctica de inmunizaciones en el mundo desde el si· glo XVIII hasta los más recientes adelantos de la ingeniería genética. La meta final ha sido disponer de un producto inmunogénico, atóxico y capaz degenerar una protección duradera. Se revisan también las características epidemiológicas de las enfermedades blanco del Programa Ampliado de Inmunizaciones; en relación a esto, se anuncian los compromisos de México hacia 1988. Los autores hacen énfasis en la alta razón beneficio/costo de estos programas de vacunación y señalan que entre estos inmunogenos el que mayor efecto ha tenido en la sobrevivencia infantil es la vacunación antisarampionosa

Señales intracelulares que intervienen en el control de la glucosa / Intracellular signals intervening in glucose control

El evento inicial para el control de la glucosa principia con la unión de la insulina a su receptor. Como resultado de esta interacción, las cadenas a y b sufren cambios conformacionales y autofosforilación en la parte carboxilo terminal de la cadena b. Sólo en estas condiciones es posible que el sustrato del receptor de la insulina (IRS) se adose a la cadena b para fosforilarse. La activación del IRS permite que la PI 3-cinasa inicie otra serie de activaciones y asociaciones de proteínas que rodean a las vesículas que contienen a los transportadores de glucosa (GLUT). En la translocación del GLUT participan proteínas que se asocian a las vesículas y proteínas asociadas en la cara interna de la membrana plasmática. Lo anterior implica no solamente asociación, sino también movilización, participación de la red del citoesqueleto y fusión de las membranas. En el metabolismo de la glucosa participan enzimas que convierten la glucosa en energía o la almacenan en forma de glucógeno. En la diabetes tipo 2, enfermedad caracterizada por la falta de control de la glucosa y resistencia a la acción de la insulina, se presentan alteraciones múltiples como disminución en la expresión del receptor de la insulina en la membrana celular, disminución generalizada en la actividad de las fosfotirosinas y activación de las serinas del IRS-1 que disminuyen la señal. Aun cuando conocemos muchas de las funciones de las proteínas involucradas para el control de la glucosa, todavía no entendemos en términos moleculares el significado de la resistencia a la insulina en los pacientes con diabetes tipo 2.

Activities of the PAHO/WHO Immunology Research and Training Center in Mexico City

Meeting of the Advisory Committe on Medical Research, 12. Pan American Health Organization; 25-29 Jun. 1973

Edad óptima de vacunación contra el sarampión / Optimal age for measles vaccination

En este trabajo se presenta una revisión de los aspectos generales de la dinámica de transmisión del sarampión y se señalan semejanzas y diferencias entre países desarrollados y en desarrollo. Se mencionan y discuten las variables epidemiológicas, demográficas y nutricionales que son relevantes para diseñar un programa óptimo de vacunación orientado a la erradicación del sarampion. Dado que en países en desarrollo no existe ninguna cohorte en la que la mayoría de los individuos sean susceptibles, se concluye que no hay una edad única a la cual haya que vacunar contra el sarampión. Finalmente, se ilustra un método sencillo para calcular la fuerza y la edad promedio de la infección, así como la edad de vacunación para el sarampión a partir de la distribución de casos por edad

Encuesta serológica de hepatitis A en niños de México / Serological survey of hepatitis A in children of Mexico

Se investigó la presencia de anticuerpos contra el virus de la hepatitis A en sueros de niños mexicanos. En 27 lactantes, 190 prescolares y 673 escolares, los sueros fueron positivos en 33, 75 y 84 por ciento respectivamente. Se encontró relación inversa entre el nivel socioeconómico y la prevalencia de sueros positivos (AU)

Encuesta serológica de hepatitis A en niños de México / Serological survey of hepatitis A in children of Mexico

Se investigó la presencia de anticuerpos contra el virus de la hepatitis A en sueros de niños mexicanos. En 27 lactantes, 190 prescolares y 673 escolares, los sueros fueron positivos en 33, 75 y 84 por ciento respectivamente. Se encontró relación inversa entre el nivel socioeconómico y la prevalencia de sueros positivos (AU)