Research progress on sex hormone-binding globulin involved in the occurrence and development of diabetes mellitus / 中国基层医药

Sex hormone-binding globulin (SHBG) is significantly associated with abnormal glucose metabolism. Low SHBG level is a risk factor for insulin resistance and the occurence of diabetes mellitus. SHBG is negatively correlated with the risk of type 2 diabetes mellitus and plays an important role in regulating insulin resistance while predicting its development. The genotype of SHBG has been found to be closely related to the occurrence of diabetes mellitus. Fatty liver and DNA methylation are also important factors mediating the relationship between SHBG and type 2 diabetes mellitus. The change in SHBG level may be related to insulin resistance by influencing hepatocyte nuclear factor 4a and regulating glucose transporter.

The Role of GLUT⁃1 in Cancer Metabolism Reprogramming / 中国生物化学与分子生物学报

In recent years, with the deepening of tumor biology research, people have a newer and more comprehensive understanding of complex tumor metabolism reprogramming. The glucose transport protein-1(GLUT-1) is a glucose transporter widely expressed in the cell membranes of various tissues and represents unusual overexpression in the plasma membrane of virous cancer cell. GLUT-1 can transport man-nose, galactose, glucosamine and ascorbic acid (AA). GLUT-1 is overexpressed in different degrees on the plasma membrane of different tumor cells. Overexpressed GLUT-1 will make tumor cells take in more glucose to reprogram the metabolic mode of cells, and at the same time, it influences the change of tumor microenvironment. And the regulation of GLUT-1 in tumors has been the focus of attention in recent years, and the upstream regulators that have been reported mainly include phosphatase and tension homolog deleted on chromosome ten (PTEN) and hypoxia inducible factor (HIF). GLUT-1 also plays an important role in tumorigenesis and development by influencing the p53 and cellular tumorigenic gene (c-Myc) pathways. The review introduces structure and function of GLUT-1, the effects of transporting different substrates in tumor metabolic reprogramming, the regulation of GLUT-1, and the current treatment of GLUT-1. Meanwhile, the review discusses mechanisms and development of the role of GLUT-1 in cancer metabolism reprogramming, and points out the existing problems to provide reference for the research of metabolism reprogramming and targeted therapy of malignant tumors.

Research progress on the antihypertensive effect of sodium-glucose synergistic transporter 2 inhibitors / 中华全科医师杂志

Diabetes mellitus is a chronic metabolic disease, in which the abnormality of glucose and lipid metabolism may cause multisystem damage. Sodium-glucose synergistic transporter 2 (SGLT2) inhibitors are a novel type of hypoglycemic drug that can lower blood sugar level by inhibiting the absorption of glucose through renal tubules. Studies have shown that SGLT2 inhibitors also have a lowering effect on blood pressure, but the mechanism is not fully elucidated. In this article the hypotensive effects of SGLT2 inhibitors and possible mechanisms are reviewed.

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications

ABSTRACT Purpose: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). Materials and Methods: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. Results: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. Conclusions: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

The Potential Cardioprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors / 임상당뇨병

The potential mechanism by which sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent cardiovascular disease (CVD) is being widely investigated. Improved insulin resistance, along with decreased body fat mass associated with SGLT2 inhibitor treatment is consistent with previously well-established factors contributing to the prevention of CVD. These factors are responsible for reduction of oxidative stress as well as improvement of systemic inflammation. Because heart failure was one of the most dramatically improved cardiovascular events in various clinical trials and because SGLT2 inhibitors promote osmotic diuresis and natriuresis, hemodynamic changes are considered as a critical mechanism responsible for the cardioprotective effect of SGLT2 inhibitors. Restored tubuloglomerular feedback by SGLT2 inhibitors might play a role in renoprotection, which in turn, leads to fewer CVDs. Finally, blood ketone body increments in response to SGLT2 inhibition might act as a “super-fuel” for salvaging the failing diabetic heart.

Expression and clinical significance of glucose transporters 1, monocarboxylate transporter 1 and monocarboxylate transporter 4 in colon cancer / 中国基层医药

Objective To investigate the correlation between the expression of glucose transporters 1 (GLUT1),monocarboxylate transporter 1 (MCT1),monocarboxylate transporter 4(MCT4) and clinical characteristics in colon cancer. Methods From January 2008 to January 2016,the carcinoma tissues of 84 cases with colon cancer after gastrointestinal surgery, and 40 samples of corresponding adjacent normal colon tissues in the First People＇s Hospital of Hangzhou were collected. The clinical data were collected. Immunohistochemistry was performed to detect the expression of GLUT1, MCT1 and MCT4, the results were analyzed. Results The positive expression rates of MCT1,GLUT1 and MCT4 in colon cancer were 54. 8% (46/84),47. 6% (40/84),58. 3% (49/84),respectively, which were significantly higher than those of the control group[12. 5% (5/40),7. 5% (3/40),15. 0% (6/40)],the differences were statistically significant (χ2=19. 987,19. 253,20. 615,all P＜0. 01). The expressions of GLUT1, MCT1,and MCT4 were not related to gender,age and tumor size,but related to lesion location,differentiation,lymph node metastasis,distant metastasis and clinical stage( GLUT1:χ2=6. 227,11. 629,10. 029,14. 817,4. 709;MCT1:χ2=6. 891,8. 615,9. 185,5. 337,16. 131;MCT4:χ2=8. 641,7. 077,12. 131,6. 917,7. 077;all P ＜0. 05). Conclusion High expression of GLUT1,MCT1 and MCT4 were observed in colon cancer. GLUT1,MCT1 and MCT4 may affect the development of colon cancer through energy metabolism pathway in colon cancer tissues.

Identification and preparation of a glycol-protein fraction AN from tea extracts and its and anti-hyperglycosemia activity / 中国中药杂志

The present study compared active ingredients of tea from different sources to select tea type and the fraction of tea extracts for the highest anti-hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected tea extract. Tea extracts were separated and enriched by molecular weight using ultra-filtration technology. The extracts were first screened by -glucosidase inhibition assay, followed by using a rat inverted intestine sac system to measure the effect on glucose transport. Both alloxan-induced diabetic rat model and high-fat diet combined with streptozotocin-induced rat diabetes mellitus model were used to study the effects of active components on blood glucose, body weight, insulin resistance. The experimental results showed that the different kinds of tea extracts had different inhibitory effects on -glucosidase, and the inhibitory effect of tea extract E on -glucosidase was stronger. The effects of different components of tea extract E also varied greatly, of which Fraction AN protein had stronger inhibitory effect on -glucosidase than other fragments, and Fraction AN protein had a strong inhibitory effect on glucose transport, reduced blood sugar and normalized insulin secretion in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the extracts might be responsible for the anti-hyperglycemic activity of tea polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on both -glucosidase activity and glucose transport by the small intestine. It also reduced blood glucose level and normalized insulin secretion in diabetic rats, and has a protective effect on diabetic rats.

Advances in placental glucose transport in hyperglycemic pregnant women / 中华围产医学杂志

As a common pregnancy complication,hyperglycemia in pregnancy has an important impact on pregnancy outcomes and the short-and long-term health of both mothers and babies.Placenta is important for maternal-fetal transport of nutrients and its capability of glucose transportation,which is influenced by the expression and regulation of glucose transporters,is crucial for hyperglycemia in pregnancy women.In this review,we summarized research results on the distribution and expression of several common placental glucose transporters in women with different types of hyperglycemia in pregnancy and their association with offspring development,as well as the main regulatory mechanisms affecting the expression of glucose transporters in order to provide evidences for understanding the mechanism of the effect of hyperglycemia in pregnancy on maternal and fetal health.

Correlation of Glut-1, Glut-3 and HK-H expression with 18F-FDG uptake in non-small cell lung cancer and pulmonary inflammatory lesions / 中华核医学与分子影像杂志

Objective To analyze the expression of glucose transport protein (Glut)-l,Glut-3 and hexokinase (HK)-Ⅱ in non-small-cell lung cancer (NSCLC) lesions and pulmonary inflammatory lesions and discuss the correlation of them with 18F-fluorodeoxyglucose (FDG) uptake.Methods Twenty-four patients with NSCLC and 22 patients with pulmonary inflammatory lesions (25 males,21 females;age range:37-81 years) who underwent PET/CT from November 2012 to May 2016 were retrospectively analyzed.All patients had surgery and were confirmed by pathology.The expression of Glut-1,Glut-3 and HK-Ⅱ in the lesions was detected by immunohistochemistry.Immunohistochemical staining scores and maximum standardized uptake value (SUVmax) were calculated.One-way analysis of variance,the least significant difference t test,two-sample t test and Spearman correlation analysis were used.Results The SUVmax of NSCLC lesions was 8.71 ± 7.62,higher than that of pulmonary inflammatory lesions (3.29 ± 2.16;t =3.220,P＜ 0.05).Immunohistochemical staining scores of Glut-1,Glut-3 and HK-Ⅱ were 3.75±0.99,4.04±1.00 and 4.00±0.78 for NSCLC lesions respectively,and were all higher than those of pulmonary inflammatory lesions (2.32±0.65,2.89±0.83,2.41±0.50;t values:5.340,5.160,8.130,all P＜0.01).The expression of Glut-1 and HK-Ⅱ was positively correlated with SUVmax in NSCLC lesions (rs values:0.414,0.457,both P＜0.05).The expression of Glut-1,Glut-3 and HK-Ⅱ was not correlated with SUVmax(rs values:0.392,0.070,-0.066,all P＞0.05),but the expression of Glut-3 was higher than that of Glut-1 and HK-Ⅱ (F=4.123,t values:0.970,0.150,all P＜0.05) in pulmonary inflammatory lesions.Conclusions The expression of Glut-1,Glut-3 and HK-Ⅱ is higher in NSCLC lesions than that in pulmonary inflammatory lesions.Glut-1 and HK-Ⅱ are the important factors for 18F-FDG uptake in NSCLC.Glut-3 may play an important role in 18F-FDG uptake in pulmonary inflammatory lesions.

Expression and Correlation of Sex Hormone-binding Globulin,Insulin Signal Transduction and Glucose Transporter Proteins in the Gestational Diabetes Mellitus Placental Tissue / 中国医科大学学报

Objective To study the expression of sex hormone-binding globulin(SHBG),insulin signaling pathway and glucose transporter in placenta of pregnant women with gestational diabetes mellitus(GDM),and to explore its role in the pathogenesis of GDM. Methods A total of 10 full-term and non-obese(BMI0.05). Results of linear correlation analysis showed that there were positive correlations between SHBG mRNA and IRS-2 mRNA(P<0.05),SHBG mRNA and PI3K p85α mRNA(P<0.05),and SHBG mRNA and GLUT-4 mRNA(P<0.05). There was also a remarkable positive correlation between IRS-2 mRNA and GLUT-4 mRNA(P<0.01). There existed negative correlations between IRS-1 mRNA and PI3K p85α mRNA(P<0.05),and IRS-1 mRNA and GLUT-3 mRNA(P<0.05). There existed a remarkable positive correlation between IRS-2 mRNA and GLUT-1 mRNA(P<0.01). Conclusion The defective receptors of insulin signaling pathway are present in GDM placental tissue. Decreased expression of SHBG may be involved in the regulation insulin signaling ,leading to a concomitant decrease expression of relevant insulin signaling components in placental tissue ,implying insulin resistance and developing GDM finally.

Effects of anti-inflammatory drugs of diacerein on glucose and lipid metabolism in type 2 diabetic rats / 医学研究生学报

Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.

Insulin signaling pathway and glucose metabolism in Alzheimer’s diseases / 国际药学研究杂志

Alzheimer’s disease AD is a degenerative metabolic disease, whose exact pathological mechanism still remains unknown. Currently, studies have found that patients in AD accompany with insulin signaling pathway impairment and cerebral glucose metabolism dysfunction. As insulin signaling pathway and cerebral glucose metabolism homeostasis play a key role in AD, some researches consider AD as“type III diabetes”. This review aims to discuss the alteration of cerebral insulin signaling pathway and glucose metabolism in AD, as well as their relationship with AD. We will also elaborate the advance in anti-AD drugs based on cerebral insulin signaling pathway.

Progress in the mechanism of blood-brain barrier dysfunction in diabetic complications / 中国药学杂志

Diabetes mellitus is closely related to the central nervous system (CNS) diseases, and it is now evident that blood-brain barrier (BBB) dysfunction plays a significant role in diabetes-dependent CNS disorders, such as stroke, vascular dementia, cognitive deficits, etc. Changes in plasma glucose levels (hyper- or hypoglycemia) have been associated with altered BBB transport functions (e.g., glucose, amino acids, etc.), the integrity of BBB, and oxidative stress in the CNS microvascular. However, the underlying causes of diabetes-induced CNS complications are multifactorial and are relatively little understood. This review focuses on the major findings and current knowledge with regard to the impact of diabetes on BBB integrity and function to explore the new research area and the new drug targets for treatment of diabetic dependent CNS complications.

Avaliação da imunoexpressão do transportador de glicose-1 em cistos radiculares e dentígeros

Dentre as lesões que levam à destruição óssea nos maxilares, os cistos odontogênicos são as mais comuns. A inflamação que participa na patogênese de alguns desses cistos pode estimular modificações no metabolismo celular energético, possibilitando a expressão do transportador de glicose-1 (GLUT-1). A partir deste contexto, o presente estudo objetiva analisar a imuno expressão do GLUT-1 em cistos radiculares (CR) e dentígeros (CD).A amostra foi constituída de 36 casos, sendo 18 de CR e 18 de CD. Foi realizado estudo morfológico para o diagnóstico histopatológico de coloração por hematoxilina & eosina (HE),bem como a análise da intensidade do infiltrado inflamatório dos CRs (leve/intenso) no aumento de 100x. Para avaliação imuno-histoquímica, foi utilizada a técnica da estreptoavidina-biotina, com o uso do anticorpo anti-GLUT-1 (GeneTex®, 1:300, citrato pH6, Pascal). A análise quantitativa foi realizada por meio de contagem percentual de células imunomarcadas em cinco campos fotografados no aumento de 400x; enquanto a análise da intensidade de imunomarcação (sem expressão/fraca expressão/forte expressão) ocorreu através da avaliação de um campo fotografado no aumento de 100x; para ambas as avaliações,utilizou-se o programa Image J. Os dados clínicos foram comparados entre grupos por meio do teste qui-quadrado de Pearson ou Exato de Fisher e por meio de Regressão Logística Multinomial. As contagens de células positivas foram analisadas por meio do teste de Mann Whineyou Kruskall-Wallis/Dunn (dados não paramétricos). Adicionalmente, utilizou-se a correlação de Spearman entre alguns grupos. Todos os testes estatísticos tiveram como baseos níveis de significância de 5%...

Odontogenic cysts are one of the most common osseous-destructive lesions in the jaws.Inflammation involved in the pathogenesis of some of these cysts can stimulate changes in theenergy cellular metabolism, enabling an increase of glucose transporter-1 expression (GLUT1).In this way, the present study aims to evaluate the immunohistochemical expression ofGLUT-1 in radicular cysts (RC) and dentigerous cysts (DC). The sample consists of 36 cases,18 RC and 18 cases of DC. Morphological study was conducted for histopathologic diagnosisby staining with HE as well as the intensity of the RCs’ inflammatory infiltrate analysis(slight/heavy) using 100x magnification. For immunohistochemical assessment, the techniquestreptavidin-biotin was used, with anti-GLUT-1 antibody (GeneTex®, 1: 300, Citrate pH 6).Quantitative analysis was performed by counting of immunostained cells in 05 photographedfields at 400x magnification. The analysis of immunostaining intensity (no expression / weakexpression / strong expression) occurred by evaluating 01 photographed field at 100xmagnification. The software Image J was used for both reviews. Clinical data between groupswere compared using Pearson's chi-square test or Fisher's exact test and through LogisticMultinomial Regression. Scores of positive cells were analyzed using the Mann-Whiney orKruskall-Wallis/Dunn test (nonparametric data). Additionally, the Spearman correlation wasused among some groups. All statistical tests were based on the significance level of 5%...

Insulin signaling pathway and glucose metabolism in Alzheimer′s diseases / 国际药学研究杂志

Alzheimer′s disease(AD)is a degenerative metabolic disease,whose exact pathological mechanism still remains unknown. Currently,studies have found that patients in AD accompany with insulin signaling pathway impairment and cerebral glu?cose metabolism dysfunction. As insulin signaling pathway and cerebral glucose metabolism homeostasis play a key role in AD ,some researches consider AD as“typeⅢdiabetes”. This review aims to discuss the alteration of cerebral insulin signaling pathway and glu?cose metabolism in AD,as well as their relationship with AD. We will also elaborate the advance in anti-AD drugs based on cerebral insulin signaling pathway.

Análisis del efecto de la sal en el desarrollo de obesidad / Analysis of the effect of salt intake on the development of obesity

Introducción: el transporte de la glucosa y de muchos aminoácidos en el intestino es realizado por el cotransportador SGLT1 únicamente si esta unido al ion sodio. La sal aporta un ion sodio por cada molécula que se consume y en los humanos su ingesta comúnmente es de diez veces más de la cantidad necesaria y generalmente se acompaña de dietas ricas en carbohidratos. Este trabajo se planteo pensando en que una estrategia simple para reducir de peso sería el disminuir la cantidad de sal en los alimentos. Objetivo: estudiar el efecto que tiene la sal en la dinámica de la absorción de glucosa y el efecto de una dieta rica en carbohidratos y sal en el desarrollo de obesidad en ratas Wistar. Métodos: para corroborar la hipótesis se evaluó el efecto de la sal en la dinámica de la absorción de la glucosa en el intestino realizando curvas de tolerancia a la glucosa con sal y sin sal. También se analizó si una dieta rica en carbohidratos y sal favorece el desarrollo de obesidad en ratas Wistar. Resultados: los experimentos mostraron que la ingesta de sal no influye en la dinámica de la absorción intestinal de la glucosa, ni en el desarrollo de obesidad en la rata Wistar. Conclusión: el sodio que de manera natural recircula desde el citoplasma de los enterocitos hacia la luz del intestino mantiene saturado al cotransportador de la glucosa SGLT1 y garantiza en todo momento el transporte de la glucosa que se ingiere en la dieta.

Introduction: Intestinal transport of glucose and many amino acids is performed by the SGLT1 cotransporter only when the latter is bound to the sodium ion. Salt contributes a sodium ion per molecule ingested. Human salt intake is often tenfold the required amount, and is generally accompanied by a carbohydrate-rich diet. The present study is based on the assumption that reducing the amount of salt in foods is a simple weight-loss strategy. Objective: Study the effect of salt on glucose absorption dynamics and the effect of a diet rich in carbohydrates and salt on the development of obesity in Wistar rats. Methods: To corroborate the hypothesis, an evaluation was conducted of the effect of salt on intestinal glucose absorption, based on glucose tolerance curves with and without salt. An analysis was also made of whether a diet rich in carbohydrates and salt leads to the development of obesity in Wistar rats. Results: Experiments showed that salt intake does not influence intestinal glucose absorption or the development of obesity in Wistar rats. Conclusion: Sodium naturally recirculating from the cytoplasm of enterocytes to the intestinal lumen keeps the SGLT1 glucose cotransporter saturated and at all times ensures the transport of the glucose ingested in the diet.

Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4 / 中国天然药物

The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro.

Correlation between Expression of Glucose Transporters in Granulosa Cells and Oocyte Quality in Women with Polycystic Ovary Syndrome

BACKGROUND: The glucose transporters (GLUTs) exhibit different tissue-specific expression. This study aimed to investigate the types of GLUTs expressed in human granulosa cells (GCs) obtained from women with polycystic ovary syndrome (PCOS) and their relationship with insulin resistance (IR) and the outcomes of in vitro maturation (IVM) of immature oocytes. METHODS: Expression of GLUTs was evaluated in GCs from women with PCOS with or without IR. Thirty-six women with PCOS undergoing an IVM program were included. Differential gene expression between the insulin sensitive (IS) and IR group was measured by reverse transcription polymerase chain reaction. RESULTS: Expression of GLUTs 1, 3, 5, 8, and 13 was constitutive, whereas expression of GLUTs 2 and 7 was not observed in human GCs. The remaining GLUTs, 4, 6, 9, 10, 11, and 12, were differentially expressed among patients according to metabolic status, such as insulin sensitivity. A higher number of GCs from patients with IR (92%) expressed GLUT6 than GCs from IS PCOS patients (46.3%). Logistic regression showed that expression of GLUTs 9, 11, and 12 correlates with rates of IVM at 48 hours, fertilization, and implantation, respectively. CONCLUSION: This is the first report describing the expression pattern of all 13 members of the GLUT family in human GCs. Results of the present study suggest that patients' insulin sensitivity regulates GLUT expression in GCs in PCOS patients, and this may control oocyte quality for IVM and subsequent processes such as fertilization and implantation in patients taking part in an in vitro fertilization program.

Análisis del efecto de la sal en el desarrollo de obesidad: ¿existe la obesidad salada? / Analysis of the effect of salt intake on the development of obesity: is there such a thing as "salty obesity"?

Objetivos: el transporte de la glucosa y de muchos aminoácidos en el intestino se realiza por el cotransportador SGLT1 únicamente si está unido al ion sodio. La sal aporta un ion sodio por cada molécula que se consume y en los humanos su ingesta comúnmente es de diez veces más de la cantidad necesaria y, por lo general, se acompaña de dietas ricas en carbohidratos. El presente proyecto evaluó, si el consumo abundante de sal en la dieta conlleva al desarrollo de obesidad. Este trabajo se planteó pensando en que una estrategia simple para reducir de peso sería el disminuir la cantidad de sal en los alimentos. Métodos: para corroborar la hipótesis se evaluó el efecto de la sal en la dinámica de la absorción de la glucosa en el intestino realizando curvas de tolerancia a la glucosa con sal y sin sal. También se analizó si una dieta rica en carbohidratos y sal favorece el desarrollo de obesidad en ratas wistar. Resultados: los experimentos mostraron que la ingesta de sal no influye en la dinámica de la absorción intestinal de la glucosa, ni en el desarrollo de obesidad en la rata wistar. Conclusión: el sodio que, de manera natural, recircula desde el citoplasma de los enterocitos hacia la luz del intestino mantiene saturado al cotransportador de la glucosa SGLT1 y garantiza, en todo momento, el transporte de la glucosa que se ingiere en la dieta.

Objectives: intestinal transport of glucose and many amino acids is performed by the SGLT1 cotransporter only when the latter is bound to the sodium ion. Salt contributes a sodium ion per molecule ingested. Human salt intake is often tenfold the required amount, and is generally accompanied by a carbohydrate-rich diet. The present paper evaluates whether an abundant salt intake leads to the development of obesity. It is based on the assumption that reducing the amount of salt in foods is a simple weight-loss strategy. Methods: to corroborate the hypothesis, an evaluation was conducted of the effect of salt on intestinal glucose absorption, based on tolerance curves for glucose with and without salt. An analysis was also made of whether a diet rich in carbohydrates and salt leads to the development of obesity in Wistar rats. Results: experiments showed that salt intake does not influence intestinal glucose absorption or the development of obesity in Wistar rats. Conclusion: sodium naturally recirculating from the cytoplasm of enterocytes to the intestinal lumen keeps the SGLT1 glucose cotransporter saturated and at all times ensures the transport of the glucose ingested in the diet.