The Na+/glucose cotransporters: from genes to therapy

Glucose enters eukaryotic cells via two types of membrane-associated carrier proteins, the Na+/glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT). The SGLT family consists of six members. Among them, the SGLT1 and SGLT2 proteins, encoded by the solute carrier genes SLC5A1 and SLC5A2, respectively, are believed to be the most important ones and have been extensively explored in studies focusing on glucose fluxes under both physiological and pathological conditions. This review considers the regulation of the expression of the SGLT promoted by protein kinases and transcription factors, as well as the alterations determined by diets of different compositions and by pathologies such as diabetes. It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria. Finally, it covers some pharmacological compounds that are being currently studied focusing on the interest of controlling glycemia by antagonizing SGLT in renal and intestinal tissues

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-&#946;1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg-1·day-1 (D0.01, N = 14), 1 mg·kg-1·day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-&#946;1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P &#8804; 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-&#946;1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy

Soccer and homosexuality: the conflicts that lie within the affective game of the coach-adolescent athlete relationship

Discussions regarding homosexuality within a sports context are mediated by emotional nuances, especially in the world of soccer, where practitioners are required to have attributes such as strength, masculinity and aggressiveness. As a consequence, this work aimed to analyze the symbolic representation of homosexual relationships between adolescent soccer players and their coaches; and, furthermore, to understand the intention behind homoerotic relationships that are established between members of the management team and its players. In this study, researchers used the life history methodology, with participation from three adolescent athletes, ages 14, 15 and 16, and three former athletes, ages 26, 28 and 45, who we called speakers. Based on the collection and analysis of research participants’ testimonies, homosexual relations were found to have occurred between athletes and coaches, or between athletes and other members of the management team, as a part of a “social contract” that is exclusively linked to their professional objectives. These relationships appear to be purely objective; authentic affective links are absent, due apparently to the transient nature of the athletes in these groups. Too, this context is usually marked by the athlete’s physical and emotional vulnerability, and the agreements he makes within this context are accompanied with moral dilemmas, because such adolescents idealize the coach as a paternal archetype.“Futebol e homossexualidade: Os conflitos que se encontram dentro do jogo afetivo da relação treinador-atleta adolescente.” As discussões a respeito da homossexualidade no contexto esportivo são mediadas por nuanças emocionais, especialmente no mundo do futebol que exige de seus praticantes atributos de força, virilidade e agressividade. Por este motivo este trabalho teve como objetivos diagnosticar existência de relações homossexuais entre atletas adolescentes da modalidade de futebol e seus técnicos e sua representação simbólica e ainda, compreender a intencionalidade das relações homoafetivas que se estabelecem entre componentes da equipe diretiva e os jogadores. Esta pesquisa é de natureza qualitativa e a técnica adotada foi a “história de vida” e a participação de três atletas adolescentes em atividade, com idade de 14, 15 e 16 anos e três ex-atletas profissionais, com idades 26, 28 e 45 anos serviram de base metodológica. A partir da análise e tratamento dos depoimentos verificou-se que ocorreram relações homossexuais nas categorias de base envolvendo técnico e atleta, ou com outros membros da equipe diretiva, como parte dos contratos sociais, ligados exclusivamente a objetivos profissionais. Estas relações parecem ser puramente objetais, não parecendo existir vínculos afetivos duradouros, aparentemente, devido à natureza transitória de atletas nesses grupos. Também, nesses ambientes, muitas vezes marcados pela vulnerabilidade física e emocional dos atletas, os acertos para as relações homossexuais são permeadas por dilemas morais, tendo em vista que os atletas adolescentes idealizam o treinador como o arquétipo paterno ideal.“El fútbol y la homosexualidad: Los conflictos que se encuentran dentro del juego afectivo de la relación atleta-entrenador de los adolescentes.” Las discusiones sobre la homosexualidad en contexto deportivo están mediadas por matices emocionales, sobre todo en el mundo del fútbol que exige a sus jugadores atributos como la fuerza, la virilidad y los jugadores. En este estudio, los investigadores utilizaron la metodología de la historia de vida, con la participación de tres atletas adolescentes, con 14, 15 y 16 años, y tres ex atletas con 26, 28 y 45 años, que llamamos ‘oradores’. Basado en la recogida y análisis de testimonios de participantes en la investigación, se encontró que las relaciones homosexuales que se han producido entre los atletas y entrenadores, o entre atletas y otros miembros del equipo de gestión, son como parte de un “contrato social” que está vinculado exclusivamente a sus objetivos profesionales. Estas relaciones parecen ser solamente como un objeto; porque a veces no hay vínculos afectivos auténticos, debido aparentemente a la naturaleza transitoria de los atletas en estos grupos. Demasiado, este contexto es generalmente marcado por la vulnerabilidad física y emocional del deportista, y los acuerdos que hace dentro de este contexto se acompañan con dilemas morales, debido a que tales adolescentes idealizan el entrenador como un arquetipo paterno. la agresividad. Por lo tanto, este estudio tuvo como objetivo diagnosticar la existencia de relaciones homosexuales entre adolescentes atletas de fútbol y sus entrenadores y la representación simbólica de estas relaciones. También comprender la intencionalidad de las relaciones homoafetivas que se intercambian entre algunos componentes del equipo directivo y(undefined

Using structural MRI to identify bipolar disorders - 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data

Low ethanol consumption increases insulin sensitivity in Wistar rats

Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control) or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v) for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT) was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05). In addition, an intravenous glucose tolerance test (IVGTT) was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05), despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved