RESUMEN
OBJECTIVE: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway. METHODS: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results. RESULTS: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1ß, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results. CONCLUSION: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP.
Asunto(s)
Fosfatasa 1 de Especificidad Dual/genética , Epilepsia/patología , Hipocampo/patología , Sistema de Señalización de MAP Quinasas/genética , Animales , Apoptosis , Butadienos/farmacología , Epilepsia/inducido químicamente , Mediadores de Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Aprendizaje por Laberinto , Nitrilos/farmacología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Aprendizaje Espacial , Memoria EspacialRESUMEN
Although epidemiologic studies suggest that dyslipidemia increases the risk of colorectal cancer (CRC), the prognostic value of blood lipid and apolipoprotein levels in CRC remains unclear. The aim of the present study was to investigate the impact of blood lipid and apolipoprotein levels on the prognosis of patients with stage III and high-risk stage II CRC undergoing curative surgery. Preoperative levels of total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, apolipoprotein A1 and apolipoprotein B (APO-B) in patients with CRC undergoing surgery were evaluated. The cut-off values of these factors were determined by the maximal x2 method and were used to classify patients into two prognostic groups: Poor and good prognosis groups. The patients prognostic values were assessed using the Kaplan-Meier curve and Cox regression analysis. In addition, the impact of these parameters on the prognosis and their predictive accuracy were evaluated using nomograms and Harrells concordance index, respectively. In total, 246 patients were included in this evaluation. Based on the cut-off points for TG (1.53 mmol/l in men and 1.58 mmol/l in women) and APO-B (0.73 mmol/l in men and women), the present study determined that both TG and APO-B were predictors of disease-free survival (DFS) and overall survival (OS). Multivariate analysis demonstrated that high TG (men, ≥1.53 mmol/l; women, ≥1.58 mmol/l) and high APO-B (≥0.73 mmol/l) levels were significantly associated with decreased DFS and OS. Nomograms that included values for TG and APO-B levels demonstrated higher predictive accuracy compared with that of nomograms without these values. These results indicated that TG and APO-B levels may be good independent prognostic biomarkers after radical CRC surgery. Therefore, adjusting these parameters to moderate levels may be beneficial.
RESUMEN
BACKGROUND: Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms. METHODS: Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1ß, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress. RESULTS: The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1ß, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05). CONCLUSION: n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.
Asunto(s)
Esofagitis Péptica/dietoterapia , Inflamación/dietoterapia , Factor 88 de Diferenciación Mieloide/biosíntesis , FN-kappa B/biosíntesis , Animales , Modelos Animales de Enfermedad , Esofagitis Péptica/genética , Esofagitis Péptica/metabolismo , Esofagitis Péptica/patología , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Aceites de Pescado/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Malondialdehído/metabolismo , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/genética , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa-1/biosíntesisRESUMEN
AIM: To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. METHOD: Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1ß, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. RESULTS: The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1ß, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). CONCLUSION: Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake.
Asunto(s)
Antiinflamatorios/administración & dosificación , Grasas de la Dieta/administración & dosificación , Esofagitis Péptica/dietoterapia , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Animales , Antiinflamatorios/farmacología , Grasas de la Dieta/farmacología , Modelos Animales de Enfermedad , Esofagitis Péptica/genética , Esofagitis Péptica/inmunología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND/AIMS: Chronic inflammatory processes and gastric contents related esophageal mucosal injury are two major characteristics of reflux esophagitis RE). This study was aimed to establish a rat model fitting RE major characteristics and to investigate the effects of mosapride, one of the 5-hydroxy tryptamine (5-HT)4 receptor agonists, on mucosal inflammation in RE. METHODOLOGY: Rat RE model was established by pyloric clip and section ligation-induced chronic acid reflux esophagitis. Animal body weight and survival was monitored. Animals were treated with 0.1 mg/kg/d, 0.5 mg/kg/d, or 2.5 mg/kg/d mosapride by gavage. Gastric emptying was examined. After two weeks, pathological changes of the esophagus were determined and endothelin-1 (ED-1) expression in esophageal tissues was evaluated by immunohistochemistry. RESULTS: No significant differences were observed in the gastric emptying of RE rats after different doses of mosapride treatment (P > 0.05). Gross examination and pathological evaluation revealed that either 0.5 mg/kg/d or 2.5 mg/kg/d mosapride treatment attenuated the mucosal inflammation of RE, but a lower mosapride dose (0.1 mg/kg/d) had limited esophagoprotective effects (P > 0.05). Mosapride treatment greatly decreased the number of ED-1 positive monocytes in the esophagus compared with sham-operated controls (P < 0.05). 5-HT4 receptor and acetylcholine (Ach) receptor antagonists effectively reversed the protective effects of mosapride (P < 0.05). CONCLUSIONS: Our results demonstrated that mosapride attenuated the mucosal inflammation of RE, suggesting that mosapride might provide esophagoprotective effects in addition to its well-known prokinetic actions.
Asunto(s)
Benzamidas/farmacología , Esofagitis Péptica/tratamiento farmacológico , Reflujo Gastroesofágico/tratamiento farmacológico , Morfolinas/farmacología , Receptores de Serotonina 5-HT4 , Agonistas del Receptor de Serotonina 5-HT4/farmacología , Animales , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Masculino , Distribución Aleatoria , RatasRESUMEN
BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. METHODS: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. RESULTS: A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. CONCLUSIONS: Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Receptores de Glucagón/antagonistas & inhibidores , Administración Oral , Anciano , China , Estudios Transversales , Femenino , Receptor del Péptido 1 Similar al Glucagón , Hemoglobina Glucada/análisis , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Congenital hypothyroidism (CH) is caused by thyroid hormone deficiency present at birth. DUOXA2 (dual oxidase maturation factor 2) is one of the prerequisites for thyroid hormone synthesis. The present study explored the novel mutations of DUOXA2 in CH patients. Genomic DNA was extracted from peripheral blood of 47 unrelated CH patients, their family members and 100 healthy controls. All 6 exons and their flanking sequences of the DUOXA2 gene were PCR amplified and sequenced. Sequencing results were compared with the standard. Compound heterozygosity with DUOXA2 gene mutations at c.413-414insA (Y138X) and c.738C>G (Y246X) was identified in one patient, and absent in 100 healthy controls. Among them, the c.413414insA (Y138X) mutation was a novel one. The patient with the c.413-414insA (Y138X) mutation had mild CH symptoms. This study is the first to report a novel c.413-414insA (Y138X) mutation for CH, thereby expanding the mutational spectrum of the DUOXA2 gene.
Asunto(s)
Hipotiroidismo Congénito/genética , Proteínas de la Membrana/genética , Secuencia de Bases , Preescolar , Exones , Femenino , Heterocigoto , Humanos , Masculino , Mutagénesis Insercional , Mutación , Linaje , Mutación PuntualRESUMEN
Endoplasmic reticulum (ER) stress is considered as a key factor in free fatty acid (FFA)-induced apoptosis. ERp46, a new member of the thioredoxin family, is highly expressed in pancreatic ß-cells and plays an important role in glucose toxicity. In this study we examined the potential role of ERp46 in palmitic acid (PA)-induced cell apoptosis and the protective role of exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor. The glucose-sensitive mouse ß-pancreatic cell line, ßTC6, was used to investigate the mechanisms of PA-induced apoptosis. Our results showed that ERp46 expression was reduced in a dose- and time-dependent manner after PA treatment. Furthermore, inhibition of ERp46 expression by small interfering (si)RNA-mediated silencing enhanced the ER stress response via three separate pathways and increased ßTC6 cell apoptosis rates. Moreover, exendin-4 reduced the ER stress response and levels of apoptosis in NC transfected cells after PA treatment, but not in cells transfected with ERp46siRNA. In conclusion, ERp46 plays a protective role in PA-induced cell apoptosis by decreasing the ER stress response and might be a novel target for anti-diabetic drugs. Exendin-4 might protect against ßTC6 cell lipoapoptosis in part by activating ERp46 signaling pathway.
Asunto(s)
Apoptosis/efectos de los fármacos , Citoprotección , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Ácido Palmítico/efectos adversos , Péptidos/farmacología , Tiorredoxinas/fisiología , Ponzoñas/farmacología , Animales , Línea Celular Tumoral , Exenatida , Receptor del Péptido 1 Similar al Glucagón , Células Secretoras de Insulina/citología , Redes y Vías Metabólicas/efectos de los fármacos , Ratones , ARN Interferente Pequeño/genética , Receptores de Glucagón/agonistas , Tiorredoxinas/genéticaRESUMEN
Chronic exposure to high concentrations of saturated fatty acids, such as palmitic acid (PA), leads to apoptosis of pancreatic ß-cells through the activation of the c-Jun N-terminal kinase (JNK) signaling pathway. This study of ß-cell lipoapoptosis was designed to investigate the roles of pancreatic-derived factor (PANDER), a pro-apoptosis cytokine-like peptide, and exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor and anti-apoptosis factor. The glucose-sensitive mouse ß-pancreatic cell line, ßTC6, was used to investigate the mechanisms of PA-induced apoptosis. Twenty-four hours of PA exposure led to increased PANDER expression in a dose- and time-dependent manner, and significantly increased phosphorylation of JNK. Treatment with the JNK-specific inhibitor SP600125 reduced the PA-induced PANDER expression. After the 24h of PA exposure, cells also underwent marked apoptosis and showed increased activation of the apoptosis protease, caspase-3. The small interfering (si)RNA-mediated silencing of PANDER gene expression significantly reduced both of these effects. When PA-treated ßTC6 cells were exposed to exogenous exendin-4, JNK activation was inhibited, PANDER expression was decreased, and the numbers of apoptotic cells were reduced. Collectively, these results demonstrated that the JNK-mediated signaling mechanism of PA-induced ß-cell apoptosis involves up-regulated expression of PANDER and activation of caspase-3. Exendin-4 may protect against lipoapoptosis by interfering with the JNK-PANDER pathway.
Asunto(s)
Apoptosis/efectos de los fármacos , Citocinas/fisiología , Citoprotección , Células Secretoras de Insulina/efectos de los fármacos , Ácido Palmítico/metabolismo , Péptidos/farmacología , Ponzoñas/farmacología , Animales , Apoptosis/genética , Línea Celular Tumoral , Citocinas/genética , Exenatida , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiología , MAP Quinasa Quinasa 4/metabolismo , Ratones , Ácido Palmítico/farmacologíaRESUMEN
BACKGROUND: Patients with knee osteoarthritis patients have problems with walking, and tend to walk slower. An important aim of knee arthroplasty is functional recovery, which should include a post-operative increase in walking speed. Still, there are several problems with measuring walking speed in groups of knee osteoarthritis patients. Nevertheless, test-retest reliability of walking speed measurements is high, and when the same investigators monitor the same subjects, it should be possible to assess the walking speed effects of knee arthroplasty. The present study reports a meta-analysis of these effects. METHODS: A total of 16 independent pre-post arthroplasty comparisons of walking speed were identified through MEDLINE, Web of Science, and PEDro, in 12 papers, involving 419 patients. RESULTS: For 0.5-5 months post-operatively, heterogeneity was too large to obtain a valid estimate of the overall effect-size. For 6-12 and 13-60 months post-operatively, heterogeneity was absent, low, or moderate (depending on estimated pre-post correlations). During these periods, subjects walked on average 0.8 standard-deviations faster than pre-operatively, which is a large effect. Meta-regression analysis revealed significant effects of time and time squared, suggesting initial improvement followed by decline. CONCLUSION: This meta-analysis revealed a large effect of arthroplasty on walking speed 6-60 months post-operatively. For the first 0.5-5 months, heterogeneity of effect-sizes precluded a valid estimate of short-term effects. Hence, patients may expect a considerable improvement of their walking speed, which, however, may take several months to occur. Meta-regression analysis suggested a small decline from 13 months post-operatively onwards.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Marcha , Osteoartritis de la Rodilla/cirugía , Caminata , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/efectos adversos , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Recuperación de la Función , Factores de Tiempo , Resultado del TratamientoRESUMEN
Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease. Many studies have indicated that transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) were involved in the pathophysiological mechanisms of DN. In addition, quercetin has been suggested to attenuate DN. In this study, we aim to examine whether quercetin ameliorates renal function through an effect on the expressions of TGF-ß1 and CTGF in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intraperitoneal injection of STZ. The diabetic rats were then randomized to diabetic group and quercetin therapy group. At the end of the 12th week, blood glucose, body weight, kidney weight/body weight, urine albumin excretion (UAE), serum creatinine (sCr), blood urea nitrogen (BUN), and creatinine clearance (Ccr) were measured. The expressions of TGF-ß1 and CTGF in the kidneys were determined using real-time PCR and Western blot method. Diabetic rats showed significant increases in blood glucose, kidney weight/body weight, UAE, sCr, BUN, and Ccr than control group. Treatment with quercetin improved these parameters except blood glucose. Compared with the control group, the expressions of TGF-ß1 and CTGF were elevated in the diabetic group. The overexpressions of TGF-ß1 and CTGF in the renal tissues of diabetic rats were attenuated by administration of quercetin. Our results suggest that quercetin improved renal function in rats with DN by inhibiting the overexpressions of TGF-ß1 and CTGF in the kidney.
Asunto(s)
Antioxidantes/uso terapéutico , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Quercetina/uso terapéutico , Factor de Crecimiento Transformador beta1/biosíntesis , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To compare the application of two different definitions of MS (IDF2005 and ATPIII2001) in this study population. According to IDF2005, evaluate the impact of body fat content and its distribution for the risk of metabolic syndrome. METHODS: The sample of 818 subjects measure the simple anthropometric parameters including body mass index (BMI), waist circumference, waist-hip ratio (WHR), and so on. Body fat mass and distribution were measured by dual-energy X-ray absorptiometry (DEXA). Quartile method is used to analyse the relevance ratio of MS in different value of BF and TF. ROC curve is used in evaluating of tipping point of BF, TF, simple body composition parameters and reliability of diagnosis. The risk of MS were analyzed by logistic regression. RESULTS: According to IDF2005, when BF, TF > or = P50. the relevance ratio of MS has a remarkable increasing (P < 0.01), its matching BMI is 24 and 23 kg/m2, according to NCEP ATPIII2001, when BF, TF > or =P75, the relevance ratio of MS has a remarkable increasing, too (P < 0.01), its matching BMI value is 26 kg/m2, BF and TF of MS patients which diagnosed by IDF2005 are lower than ATPIII2001 (P < 0.05). For each additional level of BF,the odds ratios of MS prevalence were 1.952 (male) and 2.644 (female); for each additional level of TF,the odds ratios of MS prevalence were 3. 276 (male) and 3.058 (female), BMI, WHR were not into the equation. The AUCROC which used to evaluate the exist of MS by BF and TF is larger than 0.9, and has better performance in sensitivity and specificity than BMI and WHR; the best point of contact of MS in BF is 25% (male), 35% (female), in TF is 30% (male), 38% (female). CONCLUSION: ATPIII standards may have been missed MS patients with normal high fasting blood glucose value and abdominal obesity. The application of IDF2005 standards was proved better in this population. Compared with simple anthropometric parameters, the accumulation of body fat, especially trunk fat even more harmful, to is better to identify the risk of MS in Fuzhou adults population.
Asunto(s)
Tejido Adiposo/metabolismo , Composición Corporal , Síndrome Metabólico/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/metabolismo , Medición de Riesgo , Relación Cintura-CaderaRESUMEN
OBJECTIVE: To investigate the effects of early intensive therapy on beta cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels. METHODS: A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0 - 16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia. The treatments were stopped after euglycemia had been maintained for 2 weeks. The patients were followed longitudinally on diet alone for 1 year. Intravenous glucose tolerances tests (IVGTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up. Homeostasis model assessment (HOMA) of beta cell function and insulin resistance index (HOMA-beta and HOMA-IR) were calculated. All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L = FPG < 11.1 mmol/L), stratum B (11.1 mmol/L = FPG = 16.7 mmol/L). RESULTS: More patients in stratum A achieved target glycemic control (94.4% vs 89.8%) and in shorter time [(5.9 +/- 3.8) d vs (6.9 +/- 3.6) d, P < 0.05] as compared with those in stratum B. beta cell function represented by HOMA-beta and acute insulin response (AIR) improved significantly after intensive interventions in both stratum A and B patients. However, the remission rate at 1 year was significantly higher in stratum A patients (47.8%) than those in stratum B (35.7%, P < 0.05). The patients treated with insulin (especially with CSII) had higher remission rates and better improvement of AIR at 1 year follow-up irrespective of the recruiting FPG (CSII or MDI vs OHA: 57.1%, 51.8% vs 32.8% in stratum A, P < 0.05; 44.4%, 38.7% vs 18.6% in stratum B, P < 0.05). CONCLUSIONS: Compared with OHA, early short time intensive insulin treatment had more favorable outcomes on maintaining AIR and prolonged glycemic remission in newly diagnosed type 2 diabetic patients irrespective of the recruiting FPG levels.
Asunto(s)
Glucemia , Ayuno , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangreRESUMEN
OBJECTIVE: To investigate the characteristics of the dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients. METHODS: Intravenous glucose tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic patients and 48 subjects with normal glucose tolerance (NGT) and then blood samples were collected 1, 2, 4, 6, and 10 minutes later to measure the plasma glucose and insulin to calculate the acute insulin response (AIR) and the area under the curve of insulin (AUC of insulin), homeostasis model assessment beta-cell (Homabeta), and Homa IR (insulin resistance). RESULTS: The median AIR of the type 2 diabetic patients was -33.7 pmol/L, significantly lower than that of the NGT subjects (6962.0 pmol/L, P < 0.001). The median AUC of the type 2 diabetic patients was 834.2 pmol/L, significantly lower than that of the NGT subjects (7934.7 pmol/L, P < 0.001). When the fasting plasma glucose (FPG) of the type 2 diabetic patients was above 7.0 mmol/L, the AIR value was remarkably reduced with a median level of 317.3 pmol/L, and then subsequently disappeared when the FPG was above 9.0 mmol/L. After adjustment of the insulin resistance assessed by HOMA IR, the Homabeta of the type 2 diabetic patients was reduced to be 30% that of the NGT subjects (3.7 +/- 0.9 vs 5.9 +/- 0.9, P < 0.001). Both the fasting proinsulin concentration and the ratio of fasting proinsulin to fasting insulin of the type 2 diabetic patients were significantly higher those of the NGT subjects (22.6 pmol/L +/- 14.7 pmol/L vs 11.5 pmol/L +/- 7.1 pmol/L, P < 0.001; and 30.1% +/- 20.5% vs. 12.1% +/- 9.6%, P < 0.001). CONCLUSION: The dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients is mainly represented by the disappearance of AIR and the evident decline of AUC and HOMA B, and the decrease of quality of insulin secretion.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Insulina/sangre , Islotes Pancreáticos/fisiopatología , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Islotes Pancreáticos/metabolismo , Masculino , Persona de Mediana Edad , Proinsulina/sangre , Proinsulina/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of cytokine tumor necrosis factor alpha(TNFalpha) on pancreatic beta cells apoptosis and the effect of transcription factor nuclear factor of kappa B (NF-kB) on TNFalpha-mediated apoptosis. METHODS: INS-1 cells, a pancreatic beta cell line, were cultured,and recombinant DNA technique, transfection and reinfection technology were used to obtain INS-1/IkBDeltaN cells expressing inhibitor of kB (IkB)alphaDeltaN, mutant IkBalpha (inhibitor of NF-kB). DNA fragmentation assay and fluorescence analysis using a kB-luc reporter gene were applied to observe the NF-kB activity and beta cell apoptosis. RESULTS: NF-kB activity induced by IL-Ibeta was detectable in INS-1 cells but not in INS-1/IkBDeltaN cells. After incubation of the cells with IL-1beta (10 micro g/L), TNFalpha (100 micro g/L) and interferon (IFN)gamma (100 000 U/L) for 48 hours, the combination of TNFalpha and IFNgamma induced apoptosis in INS-1 cells but not in INS-1/IkBDeltaN cells. No apoptosis was observed after incubation of INS-1 cells with IL-1beta or IFNgamma or IL-1beta plus IFNgamma. CONCLUSION: Apoptosis is one of the TNFalpha-induced beta-cell death forms. NF-kB may play an important role in the TNFalpha-mediated beta-cell apoptosis. Inhibition of NF-kB activation protects beta-cells from TNFalpha-induced apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Islotes Pancreáticos/efectos de los fármacos , FN-kappa B/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Islotes Pancreáticos/patología , Ratas , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To investigate the effect of peroxisome proliferator-activated receptor alpha and gamma (PPARalpha and PPARgamma) ligands on free fatty acid (FFA)-induced pancreatic beta-cell impairment. METHODS: Insulinoma cell line beta-cell (INS-1 cells) were treated with PPARalpha ligand (clofibrate) and PPARgamma ligands (troglitazone and thiazolidinedione). C, N diphenyl-N'-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability assay and DNA fragmentation analysis were used to evaluate the effect of PPARalpha and PPARgamma ligands on FFA-induced INS-1 cell impairment. RESULTS: The viability of INS-1 cells decreased after incubation of the cells with FFA (0.25 - 1 mmol/L) for 24 hours. FFA (1 mmol/L) was also found to induce INS-1 cell apoptosis. Comparison of the cells treated with or without clofibrate (100 micro mol/L), troglitazone (10 micro mol/L) and thiazolidinedione (100 micro mol/L), we found that these PPARalpha and PPARgamma ligands could protect INS-1 cells from the cytotoxicity of FFA, including lipoapoptosis. CONCLUSION: FFA mediates significant lipotoxicity and lipoapoptosis in beta-cells and application of PPARalpha and PPARgamma ligands might be of value in protection of beta-cells from FFA cytotoxicity.
Asunto(s)
Anticolesterolemiantes/farmacología , Cromanos/farmacología , Clofibrato/farmacología , Ácidos Grasos no Esterificados/toxicidad , Hipoglucemiantes/farmacología , Tiazolidinedionas/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Insulinoma/patología , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , TroglitazonaRESUMEN
OBJECTIVE: To study the chemical constituents in the leaf of Ligustrum delavayanum Hariot. METHOD: The constituents were isolated with column chromatographies and the structures were identified by MS, IR, UV and NMR. RESULT: Four compounds were isolated and identified as beta-sitosterol, oleanic acid, 2 alpha-hydroxyursolic acid, and acteoside. CONCLUSION: All the compounds were isolated from the plant for the first time.