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  • Rosiglitazone (peroxisome proliferator-activated receptor-gamma) counters hypertension and adverse cardiac and vascular remodeling in 2K1C hypertensive rats. 19775877

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been shown controlling blood pressure (BP) in spontaneously hypertensive rats and salt-sensitive hypertensive rats. The present study aims to test the hypothesis that PPAR-gamma agonist rosiglitazone has beneficial effects on cardiac and vascular adverse remodeling in a model of renovascular hypertension (two-kidneys-one-clip, 2K1C model). Wistar rats were divided into four groups (n=6): SHAM group, 2K1C, 2K1C+HYD (treated with hydralazine for 5 weeks) and 2K1C+ROSI (treated with rosiglitazone for 5 weeks). The left ventricle (LV), thoracic aorta (Ao) and common carotid artery (CCA) were analyzed. The BP did not show significant difference at the end of the experiment in groups 2K1C+ROSI, 2K1C+HYD and SHAM. The LV mass was smaller in 2K1C+ROSI compared with the other groups. The intima-media thickness was smaller in 2K1C+ROSI compared with untreated 2K1C ones, but not in 2K1C+HYD; 2K1C and 2K1C+HYD showed smaller Ao and CCA density of smooth muscle cell nuclei, and smaller surface density of the elastic lamellae than SHAM. The Ao and CCA circumferential wall tension and tensile stress were greater in 2K1C than in SHAM. Hypertrophied cardiomyocytes were seen in 2K1C, but not in 2K1C+ROSI and SHAM; 2K1C+ROSI had enhanced volume and length densities of intramyocardial arteries than 2K1C. The volume density of cardiac interstitium was greater in 2K1C and 2K1C+HYD than in SHAM. In conclusion, PPAR-gamma agonist rosiglitazone has beneficial effects controlling BP, reducing vascular adverse remodeling, and preserving intramyocardial vascularization in renovascular hypertensive rats (2K1C model).
    Tipo de documento:
    Referencia
    Referencia del producto:
    RI-13K
    Nombre del producto:
    Rat Insulin RIA

  • Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression. 21398515

    A mechanism-based model was developed to describe the effects of methylprednisolone (MPL), circadian rhythms, and the glucose/free fatty acid (FFA)/insulin system on leptin and adiponectin expression in white adipose tissue in rats. Fifty-four normal Wistar rats received 50 mg/kg MPL intramuscularly and were sacrificed at various times. An additional set of 54 normal Wistar rats were sacrificed at 18 time points across the 24-h light/dark cycle and served as controls. Measurements included plasma MPL, glucocorticoid receptor (GR) mRNA, leptin mRNA, adiponectin mRNA, plasma leptin, adiponectin, glucose, FFA, and insulin. MPL pharmacokinetics was described by a two-compartment model with two absorption components. All measured plasma markers and mRNA expression exhibited circadian patterns except for adiponectin and were described by Fourier harmonic functions. MPL caused significant down-regulation in GR mRNA with the nadir occurring at 5 h. MPL disrupted the circadian patterns in plasma glucose and FFA by stimulating their production. Plasma glucose and FFA subsequently caused an increase in plasma insulin. Furthermore, MPL disrupted the circadian patterns in leptin mRNA expression by stimulating its production. This rise was closely followed by an increase in plasma leptin. Both leptin mRNA and plasma leptin peaked at 12 h after MPL and eventually returned back to their circadian baselines. MPL and insulin had opposing effects on adiponectin mRNA expression and plasma adiponectin, which resulted in biphasic pharmacodynamic profiles. This small systems model quantitatively describes, integrates, and provides additional insights into various factors controlling adipokine gene expression.
    Tipo de documento:
    Referencia
    Referencia del producto:
    RI-13K
    Nombre del producto:
    Rat Insulin RIA

  • Mutation of the RIIbeta subunit of protein kinase A prevents diet-induced insulin resistance and dyslipidemia in mice. 11679434

    The mechanisms by which obesity contributes to diabetic phenotypes remain unclear. We evaluated the role of protein kinase A (PKA) signaling events in mediating diabetes associated with obesity. PKA comprises two regulatory subunits and two catalytic subunits and is activated by cAMP. The RIIbeta regulatory subunit is abundantly expressed in adipose tissue and brain. Knockout mice lacking this subunit are lean and display remarkable resistance to diet-induced obesity. We investigated whether these mice were also resistant to diet-induced diabetes and whether this effect was dependent on reduced adiposity. Mice were fed a high-fat, high-carbohydrate diet and weight gain and diabetes phenotypes were examined. RIIbeta(-/-) mice displayed decreased body weights, reduced insulin levels, improved insulin sensitivity, and improved total-body glucose disposal as compared with wild-type controls. Plasma levels of VLDL and LDL cholesterol were also reduced in high fat-fed RIIbeta(-/-) mice compared with wild-type mice. Taken together, these data demonstrate that loss of RIIbeta protects mice from diet-induced obesity, insulin resistance, and dyslipidemia.
    Tipo de documento:
    Referencia
    Referencia del producto:
    RI-13K
    Nombre del producto:
    Rat Insulin RIA

  • Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans. 11026527

    We describe a radioimmunoassay (RIA) for total leptin and a gel filtration procedure for the separation of free and bound leptin in human serum. The RIA, based on a locally prepared antibody, has a minimum detection limit of 0.9 ng/mL, a working range (CV 10%) of 2.5-50 ng/mL, inter-assay precision of 10.2, 7.2 and 8.9%CV at 7.9, 15.4 and 30.0 ng/mL, respectively, 94% recovery of exogenous leptin (range 81.1-120.6%), exhibited parallelism and demonstrated no significant cross-reactivity or interferences. A difference plot of results from this method and those from a commercially available kit (Linco Research) demonstrated satisfactory agreement up to concentrations of 50 ng/mL total leptin, with no significant bias. A gender-dependent correlation was obtained between body mass index (BMI) and total leptin (r = 0.91, P0.001, n = 75 for men; r = 0.79, P0.001, n = 72 for women), with women having higher leptin concentrations than men for any given BMI. Gel filtration studies (inter-assay precision: 4.7%CV, n = 18) demonstrated that a variable fraction (between 10% and 40%) of total leptin in serum was bound with high affinity (Keq = 1.0-1.45 x 10(9) L/mol) to a non-albumin, non-lipid macromolecule. Binding affinities were found to be similar irrespective of gender or fat mass. A significant positive correlation between free or bound leptin concentrations and BMI was obtained for both men and women (r = 0.87-0.94); free and bound leptin concentrations were also significantly higher in women (P0.01) than in men for any given BMI, and higher in obese (P0.01) than in lean individuals. We conclude that leptin 'resistance' associated with obesity cannot be accounted for by reduced free leptin concentrations in serum and that the methods described are suitable for the investigation of total, free and bound leptin for both clinical and research purposes.
    Tipo de documento:
    Referencia
    Referencia del producto:
    HL-81K
    Nombre del producto:
    Human Leptin RIA

  • Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats. 19793593

    The influence of diabetes on brain glutamate (GLU) uptake was studied in insulinopenic (streptozotocin [STZ]) and insulin-resistant (diet-induced obesity [DIO]) rat models of diabetes. In the STZ study, adult male Sprague-Dawley rats were treated with STZ (65 mg/kg intravenously) or vehicle and studied 3 weeks later. The STZ rats had elevated plasma levels of glucose, ketone bodies, and branched-chain amino acids; brain uptake of GLU was very low in both STZ and control rats, examined under conditions of normal and greatly elevated (by intravenous infusion) plasma GLU concentrations. In the DIO study, rats ingested a palatable, high-energy diet for 2 weeks and were then divided into weight tertiles: rats in the heaviest tertile were designated DIO; rats in the lightest tertile, diet-resistant (DR); and rats in the intermediate tertile, controls. The DIO and DR rats continued to consume the high-energy diet for 4 more weeks, whereas the control rats were switched to standard rat chow. All rats were studied at 6 weeks (subgroups were examined under conditions of normal or elevated plasma GLU concentrations). The DIO rats ate more food and were heavier than the DR or control rats and had higher plasma leptin levels and insulin-glucose ratios. In all diet groups, the blood-brain barrier showed very low GLU penetration and was unaffected by plasma GLU concentration. Brain GLU uptake also did not differ among the diet groups. Together, the results indicate that the blood-brain barrier remains intact to the penetration of GLU in 2 models of diabetes under the conditions examined.
    Tipo de documento:
    Referencia
    Referencia del producto:
    RI-13K
    Nombre del producto:
    Rat Insulin RIA

  • Effects of leptin supplementation to lactating Brandt\'s voles (Lasiopodomys brandtii) on the developmental responses of their offspring to a high-fat diet. 21369727

    Maternal serum leptin concentrations have been suggested as a key factor in programming growth patterns and protecting against adult metabolic disease in human offspring. However, the role of maternal leptin in the development of wild rodent offspring is not clear. We tested the hypothesis that maternal hyperleptinemia in lactating Brandt\'s voles (Lasiopodomys brandtii) can protect their offspring from the risks of high-fat-diet-induced-obesity and insulin resistance. Lactating voles were supplemented with murine leptin (0.64 μg g(-1 )day(-1)) or phosphate-buffered saline (control) on days10-17 of lactation (peak lactation). At 12 weeks of age, the female and male offspring of the two maternal groups were randomly assigned to two groups each and fed either a high-fat diet (41% of gross energy as fat) or a control diet (14% of gross energy as fat) until the age of 23 weeks. Body mass, food intake, glucose tolerance and resting metabolic rate were determined in the four offspring groups. After animals were sacrificed, organ masses and adipose tissue distribution, and serum leptin and insulin concentrations were measured. Offspring of leptin-treated mothers showed no significant differences in body mass, energy intake or energy expenditure, body composition, glucose tolerance or serum leptin and insulin concentrations from offspring of control mothers. The high-fat diet induced increases in body mass (by 23% in female and 17% in male offspring) and reduced glucose tolerance in both female and male offspring, indicative of the emergence of insulin resistance, even though digestible energy intake of the male offspring decreased on the high-fat diet. These results indicate that maternal hyperleptinemia during peak lactation in Brandt\'s voles did not protect against diet-induced obesity or glucose intolerance in their offspring.
    Tipo de documento:
    Referencia
    Referencia del producto:
    XL-85K
    Nombre del producto:
    Multi-Species Leptin RIA

  • Molecular cloning and expression of leptin in gray and harbor seal blubber, bone marrow, and lung and its potential role in marine mammal respiratory physiology. 15831765

    Leptin is a multifunctional hormone, produced predominantly in adipocytes. It regulates energy balance through its impact on appetite and fat metabolism, and its concentration indicates the size of body fat reserves. Leptin also plays a vital role in stretch-induced surfactant production during alveolar development in the fetus. The structure, expression pattern, and role of leptin have not previously been explored in marine mammals. Phocid seals undergo cyclical changes in body composition as a result of prolonged fasting and intensive foraging bouts and experience rapid, dramatic, and repeated changes in lung volume during diving. Here, we report the tissue-specific expression pattern of leptin in these animals. This is the first demonstration of leptin expression in the lung tissue of a mature mammal, in addition to its expression in the blubber and bone marrow, in common with other animals. We propose a role for leptin in seal pulmonary surfactant production, in addition to its likely role in long-term energy balance. We identify substitutions in the phocine leptin sequence in regions normally highly conserved between widely distinct vertebrate groups, and, using a purified seal leptin antiserum, we confirm the presence of the leptin protein in gray seal lung and serum fractions. Finally, we report the substantial inadequacies of using heterologous antibodies to measure leptin in unextracted gray seal serum.
    Tipo de documento:
    Referencia
    Referencia del producto:
    XL-85K
    Nombre del producto:
    Multi-Species Leptin RIA

  • Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. 15001433

    Aging mammals lose the ability to maintain energy balance, exhibiting decreased appetite (anorexia) and impaired ability to maintain body weight. To determine the contribution of hypothalamic neuropeptides, two experiments were performed in male Brown Norway rats. To assess the hypothalamic neuropeptide response to food deprivation, young (Y; 4 mo old), middle-aged (M; 13 mo), and old (O; 25 mo) rats were either ad libitum fed or fasted for 72 h (n = 10/group) and killed. Hypothalamic levels of agouti-related peptide (AgRP), proopiomelanocortin (POMC), and cocaine-amphetamine-regulated transcript (CART) mRNA were assessed by in situ hybridization. With aging, arcuate AgRP gene expression decreased and CART mRNA increased, but POMC mRNA did not change. Fasting-induced changes in gene expression of all neuropeptides studied were attenuated with aging. To test the food intake response to appetite-stimulating neuropeptides, Y, M, O, and very old (VO; 33 mo) rats (n = 4-8/group) received one intracerebroventricular injection of each of three treatments: 0.1 nmol AgRP, 2.34 nmol NPY, and saline control. AgRP increased food intake of all groups by 10-20%, compared with saline, and this effect persisted up to 7 days after injection. VO animals were more sensitive to the effects of AgRP than younger animals. In contrast, NPY increased food intake more in Y than in older animals and its effects did not last >24 h. We conclude that the mechanisms by which arcuate nucleus neurons influence appetite are differentially affected by age and speculate that the melanocortin system may be a useful target for treatment of the anorexia of aging.
    Tipo de documento:
    Referencia
    Referencia del producto:
    RI-13K
    Nombre del producto:
    Rat Insulin RIA

  • Effect of feed restriction on adipose tissue transcript concentrations in genetically lean and obese pigs. 10784183

    To determine possible genetic influences on the steady-state concentrations of several key transcription factor transcripts and the transcript concentrations for adipocyte-characteristic proteins, young, genetically obese and lean pigs were given ad libitum access or feed or were restrictively fed at 50% of ad libitum intake for 5 wk. Obese pigs were smaller and fatter than lean pigs, whether intake was ad libitum or restrictive. Plasma protein, albumin, and cholesterol concentrations were greater in obese than in lean pigs. Plasma NEFA, blood urea nitrogen, triacylglycerols, and postprandial glucose and insulin concentrations were less (P .02) in pigs fed restrictively than in pigs with ad libitum access to feed, regardless of genetic group. The adipose tissue glucose transporter 4, fatty acid synthase, and leptin transcript concentrations were greater (P .05) in obese than in lean pigs. The CCAAT/enhancer binding proteins beta and alpha, adipocyte fatty acid binding protein, hormone-sensitive lipase, and the beta1-adrenergic receptor transcript concentrations tended (P . 10) to be greater in adipose tissue from obese than in that from lean pigs. Several other transcripts were numerically greater in obese than in lean pigs. The data collectively suggest that messenger RNA concentration for several adipose tissue proteins is a contributing factor to the excess fat deposition in these obese pigs. Restricted feeding did not change the concentration of any transcript except that for adipocyte fatty acid binding protein, which was reduced. The accretion of fat was markedly reduced in the restrictively fed pigs, but this diminution does not seem to be regulated by modulation of messenger RNA concentration.
    Tipo de documento:
    Referencia
    Referencia del producto:
    HI-14K
    Nombre del producto:
    Human Insulin-Specific RIA

  • Atherogenecity of LDL and unfavorable adipokine profile in metabolically obese, normal-weight woman. 18239579

    OBJECTIVE: The relationship of visceral adiposity with adipocytokines and low-density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal-weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance. METHODS AND PROCEDURES: We examined the metabolic characteristics of 135 non-obese (BMI 25 kg/m(2)) women aged 25-64 years. Twenty-five women (BMI 25 kg/m(2) and visceral fat adiposity (VFA) > or =100 cm(2)) were classified as MONW and 25 women (BMI 25 kg/m(2) and VFA 100 cm(2)), pair-matched for age, weight, height, and menopausal status, as control group. Plasma lipid profiles and adipocytokines were evaluated in these two groups. RESULTS: MONW subjects had higher systolic (P 0.05) and diastolic blood pressure (P 0.005) and higher concentrations of triacylglycerol (TG) (P 0.005), insulin (P 0.01), and free fatty acid (FFA) (P 0.05) than control subjects. There was no significant difference between two groups in LDL-cholesterol (LDL-C) concentrations; however, MONW subjects had smaller LDL particles (P 0.01) and higher concentrations of oxidized LDL (ox-LDL) (P 0.05) compared with controls. Moreover, MONW subjects had higher concentrations of tumor necrosis factor-alpha (TNF-alpha) (P 0.05), interleukin-6 (IL-6) (P 0.05) and leptin (P 0.05), and lower plasma adiponectin concentrations (P 0.05). Higher intake of saturated fat with lower ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids (SFA) and lower fiber intake than normal subjects were found in MONW women. DISCUSSION: We found an unfavorable inflammatory profile and a more atherogenic LDL profile in MONW female subjects even in the absence of a known CVD risk factors. Moreover, MONW consumed more saturated fat and less fiber than the control group.
    Tipo de documento:
    Referencia
    Referencia del producto:
    5005