Diabetes mellitus and its complications have become a major health concern in Western countries. Increased activity of the intrarenal renin–angiotensin system (RAS) contributes to diabetic ...nephropathy (DN). We previously reported that in mesangial cells, the high glucose concentration (HG) leads to upregulation of angiotensin‐converting enzyme (ACE) messenger RNA, suggesting that ACE was modulated by angiotensin II (Ang II) release. However, this relation in the collecting duct has not yet been studied. We, therefore, aimed to evaluate RAS modulation in inner medullary collecting duct cells (IMCD) exposed to HG. The IMCD were divided into normal glucose (5 mM D‐glucose, NG), high glucose (30 mM, HG), and mannitol (30 mM, M) groups. The cells were cultured 48 hr in their respective media. The intracellular and extracellular ACE activity was measured using hippuryl‐His‐Leu as substrate via a fluorimetric assay and expression was analyzed using western blot analysis. ACE activity, intracellular (27%) and extracellular (22%), was significantly lower in the HG group than in NG and M. ACE2 activity and Ang 1–7 levels were higher in the intracellular compartment. Our data suggest that the HG cannot modify ACE synthesis in IMCD cells but can modulate its activity. The decrease in ACE activity may result in decreased levels of Ang II to protect the IMCD against proliferative and inflammatory deleterious effects of this peptide. Conversely, the increase of ACE2 generating high levels of Ang 1–7, a vasodilator peptide, suggesting that this peptide can induce glucose uptake and protect cells against oxidative stress, which can elicit insulin resistance.
Diabetes mellitus and its complications have become a major health concern in Western countries. Increased activity of the intrarenal renin–angiotensin system contributes to diabetic nephropathy (DN). The high glucose in mouse inner medullary collecting duct cells, decreased angiotensin‐converting enzyme (ACE) activity, intracellular (27%) and extracellular (22%), with no difference in ACE synthesis. Also, high glucose concentration increased ACE2 activity and Ang 1–7 levels in the intracellular. We can suggest that the high concentration of glucose in the collecting duct can activate an endogenous compensation mechanism, as ACE2/Ang 1–7 axes, that could prevent the deleterious effects triggered by increased Ang II.
Increased glucose transporter 1 (GLUT1) expression and glucose utilization that accompany pressure overload-induced hypertrophy (POH) are believed to be cardioprotective. Moreover, it has been shown ...that lifelong transgenic overexpression of GLUT1 in the heart prevents cardiac dysfunction after aortic constriction. The relevance of this model to clinical practice is unclear because of the life-long duration of increased glucose metabolism. Therefore, we sought to determine if a short-term increase in GLUT1-mediated myocardial glucose uptake would still confer cardioprotection if overexpression occurred at the onset of POH.
Mice with cardiomyocyte-specific inducible overexpression of a hemagglutinin (HA)-tagged GLUT1 transgene (G1HA) and their controls (Cont) were subjected to transverse aortic constriction (TAC) 2 days after transgene induction with doxycycline (DOX). Analysis was performed 4 weeks after TAC. Mitochondrial function, adenosine triphosphate (ATP) synthesis, and mRNA expression of oxidative phosphorylation (OXPHOS) genes were reduced in Cont mice, but were maintained in concert with increased glucose utilization in G1HA following TAC. Despite attenuated adverse remodeling in G1HA relative to control TAC mice, cardiac hypertrophy was exacerbated in these mice, and positive dP/dt (in vivo) and cardiac power (ex vivo) were equivalently decreased in Cont and G1HA TAC mice compared to shams, consistent with left ventricular dysfunction. O-GlcNAcylation of Ca2+ cycling proteins was increased in G1HA TAC hearts.
Short-term cardiac specific induction of GLUT1 at the onset of POH preserves mitochondrial function and attenuates pathological remodeling, but exacerbates the hypertrophic phenotype and is insufficient to prevent POH-induced cardiac contractile dysfunction, possibly due to impaired calcium cycling.
Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from ...severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes.
Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol.
Animals fed a hypercaloric diet exhibited obesity with increased body weight (
< 0.0001), adipocyte hypertrophy (
< 0.0001), hyperglycemia (
= 0.03), and glucose intolerance (
= 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (
< 0.0001) and glucose-stimulated insulin secretion (
= 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (
= 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets.
Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.
We investigated the kidney morphofunctional consequences of high-fat diet intake since post-weaning in adult rats.
Male Wistar rats were divided into two groups: ND (normal diet;
= 10) and HD ...(high-fat diet;
= 10). The high-fat diet was introduced post-weaned and animals were followed for 8 weeks.
HD group did not change body weight gain even though food consumption has decreased with no changes in caloric consumption. The HD group showed glucose intolerance and insulin resistance. The glomerular filtration rate (GFR) was decreased
(ND: 2.8 ± 1.01; HD: 1.1 ± 0.14 ml/min) and in the isolated perfusion method (34% of decrease). Renal histological analysis showed a retraction in glomeruli and an increase in kidney lipid deposition (ND: 1.5 ± 0.17 HD: 5.9 ± 0.06%). Furthermore, the high-fat diet consumption increased the pro-inflammatory cytokines IL-6 (ND: 1,276 ± 203; HD: 1,982 ± 47 pg/mL/mg) and IL-1b (ND: 97 ± 12 HD: 133 ± 5 pg/mL/mg) without changing anti-inflammatory cytokine IL-10.
Our study provides evidence that high-fat diet consumption leads to renal lipid accumulation, increases inflammatory cytokines, induces glomeruli retraction, and renal dysfunction. These damages observed in the kidney could be associated with an increased risk to advanced CKD in adulthood suggesting that reduction of high-fat ingestion during an early period of life can prevent metabolic disturbances and renal lipotoxicity.
Mitochondria respond to metabolic demands of the cell and to incremental damage, in part, through dynamic structural changes that include fission (fragmentation), fusion (merging of distinct ...mitochondria), autophagic degradation (mitophagy), and biogenic interactions with the endoplasmic reticulum (ER). High resolution study of mitochondrial structural and functional relationships requires rapid preservation of specimens to reduce technical artifacts coupled with quantitative assessment of mitochondrial architecture. A practical approach for assessing mitochondrial fine structure using two dimensional and three dimensional high-resolution electron microscopy is presented, and a systematic approach to measure mitochondrial architecture, including volume, length, hyperbranching, cristae morphology, and the number and extent of interaction with the ER is described. These methods are used to assess mitochondrial architecture in cells and tissue with high energy demand, including skeletal muscle cells, mouse brain tissue, and Drosophila muscles. The accuracy of assessment is validated in cells and tissue with deletion of genes involved in mitochondrial dynamics.
The search for statistical techniques and forms of graphical representation that can explain the most relevant correlations among limnological variables can help interpret phenomena in a body of ...water. The objective of the article was to propose a graphical representation of the correlations among limnological variables applied in the contributing basin of the Dr. Joao Penido reservoir, in Juiz de Fora, Minas Gerais state, Brazil. Six sections were monitored monthly from May 2012 to April 2014, analysing 15 water quality parameters and their statistical correlations. The correlations were represented graphically with the program Gephi 0.8.2-beta. The influence of organic matter (of natural and anthropogenic origin resulting from pasture runoff and sewage) on water quality was verified, with an observed increase in water quality parameters especially nitrogen and phosphorous, oxygen consumed, chemical oxygen demand, turbidity and total suspended solids. It is concluded that the correlation chart assists in the understanding of the dynamics of the water quality parameters at the different sites analysed. Key words: water resources, limnological variables, hydrographic basin A busca de tecnicas estatisticas e/ou formas de representacao grafica que consigam explicar as correlacoes mais relevantes entre as variaveis limnologicas podem auxiliar na interpretacao dos fenomenos atuantes naquele corpo d'agua. O objetivo do artigo e propor uma representacao grafica das correlacoes entre variaveis limnologicas aplicada na bacia de contribuicao da represa Dr. Joao Penido, em Juiz de Fora, Minas Gerais, Brasil. Foram monitoradas seis secoes mensalmente de maio de 2012 a abril de 2014, sendo analisados quinze parametros de qualidade da agua e estes correlacionados estatisticamente. As correlacoes foram entao representadas graficamente atraves do Programa Gephi 0.8.2-beta. Verificou-se a influencia da materia organica na qualidade da agua, de origem natural e antropica, oriundos de escoamento superficial das pastagens e do esgoto domestico, observando uma piora nos parametros de qualidade da agua com destaque para o nitrogenio e fosforo, oxigenio consumido, demanda quimica de oxigenio, turbidez e solidos suspensos totais. Conclui-se que o grafico de correlacao auxilia no entendimento da dinamica entre os parametros de qualidade da agua do local analisado. Palavras-chave: recursos hidricos, variaveis limnologicas, bacia hidrografica
An important virulence factor of Klebsiella pneumoniae is the production of capsular polysaccharide (CPS), a thick mucus layer that allows for evasion of the host's defense and creates a barrier ...against antibacterial peptides. CPS production is driven mostly by the expression of genes located in a locus called cps, and the resulting structure is used to distinguish between different serotypes (K types). In this study, we report the unique genetic organization of the cps cluster from K. pneumoniae Kp13, a clinical isolate recovered during a large outbreak of nosocomial infections that occurred in a Brazilian teaching hospital.
A pyrosequencing-based approach showed that the cps region of Kp13 (cpsKp13) is 26.4 kbp in length and contains genes common, although not universal, to other strains, such as the rmlBADC operon that codes for L-rhamnose synthesis. cpsKp13 also presents some unique features, like the inversion of the wzy gene and a unique repertoire of glycosyltransferases. In silico comparison of cpsKp13 RFLP pattern with 102 previously published cps PCR-RFLP patterns showed that cpsKp13 is distinct from the C patterns of all other K serotypes. Furthermore, in vitro serotyping showed only a weak reaction with capsular types K9 and K34. We confirm that K9 cps shares common genes with cpsKp13 such as the rmlBADC operon, but lacks features like uge and Kp13-specific glycosyltransferases, while K34 capsules contain three of the five sugars that potentially form the Kp13 CPS.
We report the first description of a cps cluster from a Brazilian clinical isolate of a KPC-producing K. pneumoniae. The gathered data including K-serotyping support that Kp13's K-antigen belongs to a novel capsular serotype. The CPS of Kp13 probably includes L-rhamnose and D-galacturonate in its structure, among other residues. Because genes involved in L-rhamnose biosynthesis are absent in humans, this pathway may represent potential targets for the development of antimicrobial agents. Studying the capsular serotypes of clinical isolates is of great importance for further development of vaccines and/or novel therapeutic agents. The distribution of K-types among multidrug-resistant isolates is unknown, but our findings may encourage scientists to perform K-antigen typing of KPC-producing strains worldwide.
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