Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets.

An over-activation of the mechanistic target of rapamycin (mTOR) pathway promotes senescence and age-related diseases like type 2 diabetes. Besides, the regenerative potential of pancreatic islets deteriorates with aging. Nevertheless, the role of mTOR on senescence promoted by metabolic stress in islet cells as well as its relevance for electrophysiological aspects is not yet known. Here, we investigated whether parameters suggested to be indicative for senescence are induced in vitro in mouse islet cells by glucotoxicity and if mTOR inhibition plays a protective role against this. Islet cells exhibit a significant increase (~ 76%) in senescence-associated beta-galactosidase (SA-beta-gal) activity after exposure to glucotoxicity for 72 h. Glucotoxicity does not markedly influence p16INK4a protein within 72 h, but p16INK4a levels increase significantly after a 7-days incubation period. mTOR inhibition with a low rapamycin concentration (1 nM) entirely prevents the glucotoxicity-mediated increase of SA-beta-gal and p16INK4a. At the functional level, reactive oxygen species, calcium homeostasis, and electrical activity are disturbed by glucotoxicity, and rapamycin fails to prevent this. In contrast, rapamycin significantly attenuates the insulin hypersecretion promoted by glucotoxicity by modifying the mRNA levels of Vamp2 and Snap25 genes, related to insulin exocytosis. Our data indicate an influence of glucotoxicity on pancreatic islet-cell senescence and a reduction of the senescence markers by mTOR inhibition, which is relevant to preserve the regenerative potential of the islets. Decreasing the influence of mTOR on islet cells exposed to glucotoxicity attenuates insulin hypersecretion, but is not sufficient to prevent electrophysiological disturbances, indicating the involvement of mTOR-independent mechanisms.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity.

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.

Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease.

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-ß/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

Maize Flavonoid Biosynthesis, Regulation, and Human Health Relevance: A Review.

Maize is one of the most important crops for human and animal consumption and contains a chemical arsenal essential for survival: flavonoids. Moreover, flavonoids are well known for their beneficial effects on human health. In this review, we decided to organize the information about maize flavonoids into three sections. In the first section, we include updated information about the enzymatic pathway of maize flavonoids. We describe a total of twenty-one genes for the flavonoid pathway of maize. The first three genes participate in the general phenylpropanoid pathway. Four genes are common biosynthetic early genes for flavonoids, and fourteen are specific genes for the flavonoid subgroups, the anthocyanins, and flavone C-glycosides. The second section explains the tissue accumulation and regulation of flavonoids by environmental factors affecting the expression of the MYB-bHLH-WD40 (MBW) transcriptional complex. The study of transcription factors of the MBW complex is fundamental for understanding how the flavonoid profiles generate a palette of colors in the plant tissues. Finally, we also include an update of the biological activities of C3G, the major maize anthocyanin, including anticancer, antidiabetic, and antioxidant effects, among others. This review intends to disclose and integrate the existing knowledge regarding maize flavonoid pigmentation and its relevance in the human health sector.

Effect of Lupinus rotundiflorus gamma conglutin treatment on JNK1 gene expression and protein activation in a rat model of type 2 diabetes.

CONTEXT: Gamma conglutin (Cγ) from lupine species represents a potential complementary treatment for type 2 diabetes mellitus (T2DM) because of its hypoglycaemic effect. However, its underlying mechanism of action is not fully known. OBJECTIVE: To evaluate whether Cγ from Lupinus rotundiflorus M. E. Jones (Fabaceae) modulates c-Jun N-terminal kinase 1 (JNK1) expression and activation in a T2DM rat model. MATERIALS AND METHODS: Gamma conglutin isolated from L. rotundiflorus seeds was characterized by SDS-PAGE. Fifteen Wistar rats with streptozotocin-induced T2DM (HG) were randomized into three groups (n = 5): vehicle administration (HG-Ctrl), oral treatment with Cγ (120 mg/kg/day) (HG-Lr) for one week, and treatment with metformin (300 mg/kg/day) (HG-Met); a healthy group (Ctrl, n = 5) was included as control. The levels of glucose and biomarkers of renal and hepatic function were measured pre- and post-treatment. Hepatic Jnk1 expression and phosphorylation of JNK1 were evaluated by qRT-PCR and western blot, respectively. RESULTS: Oral treatment with either Cγ or metformin reduced serum glucose level to 86.30 and 74.80 mg/dL, respectively (p ˂ 0.05), from the basal levels. Jnk1 expression was 0.65- and 0.54-fold lower (p ˂ 0.05) in the HG-Lr and HG-Met groups, respectively, than in HG-Ctrl. Treatment with Cγ decreased JNK1 phosphorylation. However, Cγ did not change the levels of kidney and liver biomarkers. DISCUSSION AND CONCLUSIONS: Treatment with Cγ from L. rotundiflorus inhibited Jnk1 expression, in vivo, suggesting JNK1 as a potential therapeutic target in diabetes and revealing one mechanism underlying the hypoglycaemic effect of lupine Cγ. Nevertheless, further studies are required.

Lupinus albus Conglutin Gamma Modifies the Gene Expressions of Enzymes Involved in Glucose Hepatic Production In Vivo.

Lupinus albus seeds contain conglutin gamma (Cγ) protein, which exerts a hypoglycemic effect and positively modifies proteins involved in glucose homeostasis. Cγ could potentially be used to manage patients with impaired glucose metabolism, but there remains a need to evaluate its effects on hepatic glucose production. The present study aimed to analyze G6pc, Fbp1, and Pck1 gene expressions in two experimental animal models of impaired glucose metabolism. We also evaluated hepatic and renal tissue integrity following Cγ treatment. To generate an insulin resistance model, male Wistar rats were provided 30% sucrose solution ad libitum for 20 weeks. To generate a type 2 diabetes model (STZ), five-day-old rats were intraperitoneally injected with streptozotocin (150 mg/kg). Each animal model was randomized into three subgroups that received the following oral treatments daily for one week: 0.9% w/v NaCl (vehicle; IR-Ctrl and STZ-Ctrl); metformin 300 mg/kg (IR-Met and STZ-Met); and Cγ 150 mg/kg (IR-Cγ and STZ-Cγ). Biochemical parameters were assessed pre- and post-treatment using colorimetric or enzymatic methods. We also performed histological analysis of hepatic and renal tissue. G6pc, Fbp1, and Pck1 gene expressions were quantified using real-time PCR. No histological changes were observed in any group. Post-treatment G6pc gene expression was decreased in the IR-Cγ and STZ-Cγ groups. Post-treatment Fbp1 and Pck1 gene expressions were reduced in the IR-Cγ group but increased in STZ-Cγ animals. Overall, these findings suggest that Cγ is involved in reducing hepatic glucose production, mainly through G6pc inhibition in impaired glucose metabolism disorders.

[Glucotransporters: clinical, molecular and genetic aspects]. / Glucotransportadores (GLUT): Aspectos clínicos, moleculares y genéticos.

Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches.

Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression.

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca(2+) action potentials. Determination of the current through ATP-dependent K⁺ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

Administration of Lupinus albus gamma conglutin (Cγ) to n5 STZ rats augmented Ins-1 gene expression and pancreatic insulin content.

Several studies support the health-promoting benefits of lupins, particularly lupin proteins. It has been demonstrated that Lupinus albus gamma conglutin (Cγ) protein lowered blood glucose levels; thus, Cγ showed promise as a new anti-diabetic compound for type 2 diabetes (T2D) treatment. The aim of this study was to evaluate the effect of Cγ on Ins-1 gene expression and on pancreatic insulin content in streptozotocin-mediated diabetic rats. Cγ was isolated from Lupinus albus seeds. Its identification was confirmed with polyacrylamide gel electrophoresis under native and denaturing conditions. We used streptozotocin (STZ) to induce T2D on the 5th day of life of newborn male Wistar rats (n5-STZ). After 20 weeks post-induction, these animals (glycemia > 200 mg/dL) were randomly assigned to three groups that received the following one-week treatments: vehicle, 0.90% w/v NaCl (n5 STZ-Ctrl); glibenclamide, 10 mg/kg (n5 STZ-Glib); or Cγ, 120 mg/kg (n5 STZ-Cγ). Glucose and insulin levels were measured before and after treatment. Ins-1 gene expression was quantified using real time polymerase chain reaction and the pancreatic insulin content was evaluated with immunohistochemistry. Post-treatment, the n5 STZ-Cγ and n5 STZ-Glib groups showed reductions in glucose, increments in serum insulin, and increases in Ins-1 gene expression and beta cell insulin content compared to the n5 STZ-Ctrl group. The results showed that Cγ had beneficial effects on Ins-1 gene expression and pancreatic insulin content. These biological effects of Cγ strengthen its promising potential as a nutraceutical and/or new agent for controlling hyperglycemia.

Molecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review.

The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-ß/Smad or Wnt/ß-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.

An Update on Viral Hepatitis B and C in Mexico: Advances and Pitfalls in Eradication Strategies.

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections' elimination.

Reduction of lns-1 gene expression and tissue insulin levels in n5-STZ rats.

OBJECTIVE: The high global incidence of type 2 diabetes has challenged researchers to establish animal models that resemble the chronic stage observed in type 2 diabetes patients. One such model is induced by neonatal streptozotocin (n-STZ) administration to rat pups at 0, 2, or 5 days after birth. In this study, we assessed lns-1 gene expression and tissue insulin levels as well as serum concentration of glucose and insulin, insulin resistance, and histological changes of the islets of Langerhans in n5-STZ rats after 20-weeks post-induction. METHODS: Wistar rat pups were randomly distributed into a control group and a streptozotocin-induced group. Experimental induction involved a single intraperitoneal injection of streptozotocin (150 mg/kg) into neonates at five days after birth. RESULTS: At 20 weeks post-induction, streptozotocin-induced rats exhibited increased serum glucose levels, reduced serum insulin levels, impaired glucose metabolism and insulin resistance compared to control rats. Histologically, streptozotocin-induced rats exhibited atrophic islets, vacuolization, and significantly fewer insulin-positive cells. lns-1 gene expression was significantly decreased in n5-STZ rats in comparison to the control group. CONCLUSION: Our findings support that the n5-STZ model 20 weeks post-induction represents an appropriate experimental tool to study T2D and to evaluate novel therapeutic agents and targets that involve insulin gene expression and secretion, as well as complications caused by chronic diabetes.

Combined Gamma Conglutin and Lupanine Treatment Exhibits In Vivo an Enhanced Antidiabetic Effect by Modulating the Liver Gene Expression Profile.

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combining both compounds and the effective dose of the combination have not been assessed. Moreover, the resulting gene expression profile from this novel combination remains to be explored. Therefore, we aimed to evaluate different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the higher antidiabetic effect on a T2D rat model. Later, we administered the selected dose combination during a week. Lastly, we evaluated biochemical parameters and liver gene expression profile using DNA microarrays and bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine significantly reduced glycemia and lipid levels. Moreover, this treatment positively influenced the expression of Pdk4, G6pc, Foxo1, Foxo3, Ppargc1a, Serpine1, Myc, Slc37a4, Irs2, and Igfbp1 genes. The biological processes associated with these genes are oxidative stress, apoptosis regulation, and glucose and fatty-acid homeostasis. For the first time, we report the beneficial in vivo effect of the combination of two functional lupin compounds. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combined treatment.

Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function.

BACKGROUND: Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico. METHODS: Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child's Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant. CONCLUSIONS: In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics.

Cladodes from Nopalea cochenillifera (L.) Salm-Dyck (Cactaceae) attenuate postprandial glycaemia without markedly influencing α-glucosidase activity.

Although the cladodes of Nopalea cochenillifera are used in Mexican traditional medicine to treat diabetes and various other diseases, its antihyperglycaemic properties, phenolic content, and antioxidant activity are not well documented. Thus, we determined the activity of a single dose of fresh, blended cladodes on postprandial glycaemia in rats after a starch load. We prepared a methanolic extract of N. cochenillifera cladodes and measured its phenolic content, antioxidant capacity, and α-glucosidase inhibitory activity. The antihyperglycaemic effect of blended cladodes was similar to that of acarbose when considering the changes in glucose levels from baseline. Furthermore, the methanolic extract contained a considerable amount of phenolic compounds and exhibited antioxidant activity in the DPPH assay, but did not markedly inhibit α-glucosidase and had a low antioxidant effect in the ABTS test.

[Metabolic profile and concentration of ghrelin and obestatin in children and adolescents with obesity]. / Perfil metabólico, concentración de grelina y obestatina en niños y adolescentes con obesidad.

Background: It has been pointed out that ghrelin and obestatin could have an impact on the genesis of obesity, since they estimulate and inhibit apetite and, therefore, food consumption. Objective: To compare the metabolic profile, lipid profile and the concentrations of ghrelin and obestatin in children with normal weight or obesity. Material and methods: Cross-sectional design with 97 normal weight or obese children, 6 to 18 years of age, who did not present systemic diseases. The serum concentrations of glucose, insulin, total cholesterol, triglycerides, high (HDL), low (LDL) and very low density (VLDL) lipoproteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), ghrelin and obestatin were determined. Descriptive statistics were performed. Student's t test was used to compare groups, and correlation coefficients of ghrelin and obestatin values with biochemical and anthropometric variables. A p value of ≤ 0.05 was significant. Results: 55 children with normal weight and 42 with obesity were included; mean age was 10.7 years. Triglycerides, LDL, VLDL, ALT and insulin were higher, and HDL lower in obese children (p < 0.05). Ghrelin values were higher in normal weight children (p < 0.05), and there was no difference in obestatin values. Conclusions: The lower concentration of ghrelin in obese children may indicate a negative feedback to regulate energy consumption. Children and adolescents with obesity show metabolic and lipid profile alterations that place them at risk of early development of cardiovascular risk factors.

Introducción: se ha señalado que la grelina y la obestatina podrían incidir en la génesis de la obesidad al estimular o inhibir el apetito y, por ende, el consumo de alimentos. Objetivo: comparar el perfil metabólico, el perfil de lípidos y las concentraciones de grelina y obestatina en niños con normopeso u obesidad. Material y métodos: diseño transversal con 97 niños de 6 a 18 años con normopeso u obesidad que no presentaran enfermedades sistémicas. Se determinaron las concentraciones séricas de glucosa, insulina, colesterol total, triglicéridos, lipoproteínas de colesterol de alta (HDL), baja (LDL) y muy baja densidad (VLDL), aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), grelina y obestatina. Se usó estadística descriptiva. Se utilizó la prueba t de Student para comparar grupos, y coeficientes de correlación de los valores de grelina y obestatina con las variables bioquímicas y antropométricas. Un valor de p ≤ 0.05 fue significativo. Resultados: se incluyeron 55 niños con normopeso y 42 con obesidad; la edad promedio fue de 10.7 años. Los triglicéridos, LDL, VLDL, ALT y la insulina fueron superiores, y el HDL inferior en niños con obesidad (p < 0.05). Los valores de la grelina fueron superiores en niños con normopeso (p < 0.05) y no hubo diferencia en los de la obestatina. Conclusiones: la menor concentración de grelina en niños con obesidad puede indicar una retroalimentación negativa para regular el consumo de energía. Los niños y adolescentes con obesidad muestran alteraciones metabólicas y del perfil de lípidos que los ponen en riesgo de desarrollar tempranamente factores de riesgo cardiovascular.

TGF-ß1 serum concentration as a complementary diagnostic biomarker of lung cancer: establishment of a cut-point value.

UNLABELLED: Lung cancer is a malignant disease with increasing mortality rates. Cytokines play a role in normal cell growth regulation and differentiation and are also implicated in malignant disease. Among these cytokines, Transforming Growth Factor ß type 1 (TGF-ß1) acts as a tumor promoter in malignant cells. Several clinical studies have found high levels of TGF-ß1 in various cancer types. The aim of this study was to establish a TGF-ß1 cut-off point as a complementary diagnostic tool in lung cancer detection. Therefore, 72 clinically well-characterized individuals were studied, 41 lung cancer patients and 31 healthy subjects. Serum TGF-ß1 concentration was measured by an enzyme-linked immunosorbent assay (ELISA). We compared statistically the serum TGF-ß1 concentration between both groups with analysis of variance, linear regression and receiver operating curve analysis. We observed that lung cancer patients produced higher TGF-ß1 levels than healthy individuals (37,225±9,436 vs. 28,416±9,324 pg/ml, P<0.001). The cut-point diagnostic value was 30,500 pg/ml with 80.5% sensitivity, 64.5% specificity and odds ratio: 7.5, 95% CI: 2.6-21.8. CONCLUSIONS: We found significantly higher TGF-ß1 levels in lung cancer patients than in healthy individuals. We propose the measurement of serum TGF-ß1 levels as a complementary diagnostic test in lung cancer detection.

Glucokinase activation as antidiabetic therapy: effect of nutraceuticals and phytochemicals on glucokinase gene expression and enzymatic activity.

Diabetes represents an important public health problem. Recently, new molecular targets have been identified and exploited to treat this disease. Due to its pivotal role in glucose homeostasis, glucokinase (GCK) is a promising target for the development of novel antidiabetic drugs; however, pharmacological agents that modulate GCK activity have been linked to undesirable side-effects, limiting its use. Interestingly, plants might be a valuable source of new therapeutic compounds with GCK-activating properties and presumably no adverse effects. In this review, we describe biochemical characteristics related to the physiological and pathological importance of GCK, as well as the mechanisms involved in its regulation at different molecular levels. Posteriorly, we present a compendium of findings supporting the potential use of nutraceuticals and phytochemicals in the management of diabetes through modulation of GCK expression and activity. Finally, we propose critical aspects to keep in mind when designing experiments to evaluate GCK modulation properly.

Lupin protein isolate improves insulin sensitivity and steatohepatitis in vivo and modulates the expression of the Fasn, Gys2, and Gsk3b genes.

Although studies on lupin protein isolate (LPI) have indicated the presence of a preventive effect on insulin resistance (IR) and lipid disturbances, their influence on established pathological traits has received little attention. Here, we evaluated the in vivo effects of LPI on IR and steatohepatitis as well as its influence on genes involved in lipid and carbohydrate metabolism. We first induced IR and steatohepatitis in rats by maintaining them on a high-fat diet for 5 weeks. Thereafter, we administered LPI to the rats daily for 3 weeks. LPI improved insulin sensitivity (AUC: 6,777 ± 232 vs. 4,971 ± 379, p < .05, pre- vs. post-treatment values) and reduced glucose and triglyceride levels by one-third. In addition, LPI-treated rats exhibited attenuated steatohepatitis. At the molecular level, LPI treatment reduced liver Fasn gene expression substantially but increased Gys2 and Gsk3b levels. We concluded that the hypolipidemic and hypoglycemic activities of LPI may be caused by reduced liver lipogenesis and modulation of insulin sensitization mechanisms.