RESUMO
BACKGROUND: High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the ß-cell line MIN-6. METHODS: We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line. RESULTS: Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux. CONCLUSIONS: HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.
Assuntos
Colesterol/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Lipoproteínas HDL/sangue , Adulto , Animais , Linhagem Celular Tumoral , Feminino , Glucose/farmacologia , Humanos , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , PrognósticoRESUMO
Gastric cancer is one of the most frequent neoplasias in the digestive tract and is the result of premalignant lesion progression in the majority of cases. Opportune detection of those lesions is relevant, given that timely treatment offers the possibility of cure. There is no consensus in Mexico on the early detection of gastric cancer, and therefore, the Asociación Mexicana de Gastroenterología brought together a group of experts and produced the "Mexican consensus on the detection and treatment of early gastric cancer" to establish useful recommendations for the medical community. The Delphi methodology was employed, and 38 recommendations related to early gastric cancer were formulated. The consensus defines early gastric cancer as that which at diagnosis is limited to the mucosa and submucosa, irrespective of lymph node metástasis. In Mexico, as in other parts of the world, factors associated with early gastric cancer include Helicobacter pylori infection, a family history of the disease, smoking, and diet. Chromoendoscopy, magnification endoscopy, and equipment-based image-enhanced endoscopy are recommended for making the diagnosis, and accurate histopathologic diagnosis is invaluable for making therapeutic decisions. The endoscopic treatment of early gastric cancer, whether dissection or resection of the mucosa, should be preferred to surgical management, when similar oncologic cure results can be obtained. Endoscopic surveillance should be individualized.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Terapia Combinada , Técnica Delphi , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/normas , Gastroscopia/métodos , Gastroscopia/normas , Humanos , México/epidemiologia , Estadiamento de Neoplasias , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. METHODS: Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. RESULTS: In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs (r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score (r = 0.514, p = 0.001), anti-dsDNA antibodies (r = 0.467, p = 0.004), the rate of glomerular filtration descent (r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index (r = 0.581, p = 0.004), fibrinoid necrosis (r = 0.603, p = 0.002), and cellular crescents (r = 0.486, p = 0.019). CONCLUSIONS: In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.
Assuntos
Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Proteína HMGB1/sangue , Humanos , Nefrite Lúpica/sangue , Masculino , Índice de Gravidade de Doença , Adulto JovemRESUMO
Cholesteryl ester transfer protein (CETP) has been shown to transfer cholesteryl esters among plasma lipoproteins. However, when reconstituted into phosphatidylcholine liposomes, the 74,000 protein mediates above non-specific values the transfer of HDL bound [3H]cholesterol into the artificial membrane system. Employing the known cDNA sequence of CETP, we synthesized a series of oligonucleotides with specific sequences for different regions of CETP and RNA isolated from tissues known to be producers of CETP (liver), and tissues not design to synthesize and secrete CETP (ovary, lung, intestine and heart). Hybridization experiments showed that independently of the type of tissue tested CETP sequences were found. It is suggested that a membrane form of CETP might have important repercussions locally.