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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Brown adipocytes were isolated from the interscapular depot of male rats maintained at approx. 21 degrees C. In some experiments parallel studies were made with white adipocytes from the epididymal depot. 2. Insulin increased and noradrenaline decreased [U-14C]glucose incorporation into fatty acids by brown adipocytes. Brown adipocytes differed from white adipocytes in that exogenous fatty acid (palmitate) substantially decreased fatty acid synthesis from glucose. Both noradrenaline and insulin increased lactate + pyruvate formation by brown adipocytes. Brown adipocytes converted a greater proportion of metabolized glucose into lactate + pyruvate and a smaller proportion into fatty acids than did white adipocytes. 3. In brown adipocytes, when fatty acid synthesis from [U-14C]glucose was decreased by noradrenaline or palmitate, incorporation of 3H2O into fatty acids was also decreased to an extent which would not support proposals for extensive recycling into fatty acid synthesis of acetyl-CoA derived from fatty acid oxidation. 4. In the absence of glucose, [U-14C]lactate was a poor substrate for lipogenesis in brown adipocytes, but its use was facilitated by glucose. When brown adipocytes were incubated with 1 mM-lactate + 5 mM-glucose, lactate-derived carbon generally provided at least 50% of the precursor for fatty acid synthesis. 5. Both insulin and noradrenaline increased [U-14C]glucose conversion into CO2 by brown adipocytes (incubated in the presence of lactate) and, in combination, stimulation of glucose oxidation by these two agents showed synergism. Rates of 14CO2 formation from glucose by brown adipocytes were relatively small compared with maximum rates of oxygen consumption by these cells, suggesting that glucose is unlikely to be a major substrate for thermogenesis. 6. Brown adipocytes from 6-week-old rats had considerably lower maximum rates of fatty acid synthesis, relative to cell DNA content, than white adipocytes. By contrast, rates of fatty acid synthesis from 3H2O in vivo were similar in the interscapular and epididymal fat depots. Expressed relative to activities of fatty acid synthase or ATP citrate lyase, however, brown adipocytes synthesized fatty acids as effectively as did white adipocytes. It is suggested that the cells most active in fatty acid synthesis in the brown adipose tissue are not recovered fully in the adipocyte fraction during cell isolation. Differences in rates of fatty acid synthesis between brown and white adipocytes were less apparent at 10 weeks of age.
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PMID:Lipogenesis in rat brown adipocytes. Effects of insulin and noradrenaline, contributions from glucose and lactate as precursors and comparisons with white adipocytes. 313 22

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.
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PMID:Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. 1037 71

It has been recently reported that increased hematocrit and hemoglobin values often accompany insulin resistance and compensatory hyperinsulinemia in humans. In the current study, we analyzed the relationship between hematocrit/hemoglobin on the one hand and insulin resistance, dyslipidemia, and hypertension on the other hand in HXB/BXH recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the Brown Norway (BN) rat. The SHR progenitor strain had a significantly increased hematocrit values and it was also hypertensive and insulin-resistant when compared with the BN progenitor. The distribution of hematocrit and hemoglobin values among RI strains was continuous, suggesting a polygenic mode of inheritance. Analysis of RI strains revealed that hemoglobin was negatively correlated with insulin and insulin/glucose ratio, and that hematocrit was negatively correlated with insulin-stimulated glucose uptake in isolated adipocytes. There was no relationship between hematological parameters and blood pressure or lipid phenotypes in RI strains. The findings of the current study suggest that hematocrit and hemoglobin values might be added to the clustering variables related to the insulin resistance syndrome in the SHR strain.
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PMID:Hematocrit and hemoglobin values are negatively correlated with insulin resistance in spontaneous hypertension. 1073 21

Aging in men is associated with a decline in trophic factors such as testosterone (T), alterations in body composition and impaired energy and body weight regulation. We performed studies to investigate the mechanisms underlying age-related changes in the neuroendocrine control of testis function, body composition, food intake and body weight in the Brown Norway (BN) rat. We found that similar to aging men, male BN rats demonstrate both primary and secondary testicular failure with aging without confounding age-related tumors, hormonal changes and systemic illnesses. With aging, these animals have blunted circadian variations in luteinizing hormone (LH) and T, and decreased hypothalamic gonadotropin-releasing hormone (GnRH) synthetic capacity with preserved pituitary gonadotropin responses to GnRH. We found that aging male BN rats have increased peripheral and visceral adiposity associated with increased insulin and leptin levels, and decreased relative lean body mass and muscle mass. We found that these rats exhibit reduced food intake and body weight gain associated with decreased hypothalamic neuropeptide Y (NPY) gene expression in the arcuate nucleus (ARC), both during ad-libitum feeding and after a 72-h fast. Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted food intake and body weight gain response to fasting without affecting basal ARC NPY gene expression. These findings suggested that hyperinsulinemia and/or hyperleptinemia associated with aging may contribute to the age-related impairment in energy and weight regulation. Our studies suggest that the aging male BN rat is an excellent model to investigate the mechanisms underlying the age-associated changes in the neuroendocrine control of body composition, energy intake and body weight.
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PMID:Aging and the neuroendocrine regulation of reproduction and body weight. 1111 6

Compared to younger animals, aged male Brown Norway (BN) rats demonstrate increased body fat and serum insulin, and lower prepro-neuropeptide Y (ppNPY) mRNA content in the arcuate nucleus (ARC), and blunted food intake (FI) and body weight (BW) gain in response to a 72 h fast. Since centrally administered insulin decreases FI and weight of young rats and inhibits fasting-induced increases of NPY gene expression, we hypothesized that hyperinsulinemia in old rats contributes to an age-related central dysregulation of energy balance. Young, middle-aged and old BN rats were fed chow with troglitazone (Trog; 200 mg/kg BW/d) or without drug for 75 d (Experiment 1) or 66 d (Experiment 2). Rats were then fasted for 72 h, refed for 2 weeks and sacrificed after an overnight fast (Experiment 1) or fasted for 72 h and sacrificed (Experiment 2). Serum insulin and leptin were measured from trunk blood and brains were analyzed for ppNPY mRNA by in situ hybridization. In Experiment 1, troglitazone treatment resulted in increased post-fast weight gain, rate of gain and FI in old rats. Troglitazone decreased serum insulin by 50% in old rats, while leptin levels decreased 20-30% in all age groups in Experiment 1. No differences in serum insulin or leptin were detectable with troglitazone treatment in Experiment 2, due to the extreme suppression caused by the 72 h fast. Troglitazone treatment did not increase ARC NPY gene expression either after a 72 h fast and re-feeding for 2 weeks (Experiment 1) or immediately after a 72 h fast (Experiment 2). These findings suggest that increased insulin levels may contribute to age-related impairments of FI and BW regulation. However, improvements in these defects in energy regulation induced by troglitazone do not appear to result from changes in NPY gene expression, and may be due to alterations in other hypothalamic neuropeptides that regulate energy balance.
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PMID:Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression. 1190 85

The spontaneous hypertensive rat (SHR) is a widely studied model of essential hypertension and has been reported to exhibit alterations in carbohydrate and lipid metabolism. Genetic linkage studies implicated that SHR carries deletion variant of Cd36 gene of chromosome 4, the gene that encodes fatty acid transporter. Thus it could be possible that primary genetic defect in SHR is compromised tissue utilization of fatty acid that would form the basis for the pathogenesis of hyperinsulinemia, insulin resistance and insulin-mediated responses. We measured both the hemodynamic and metabolic responses to insulin in SHR in comparison with the chromosome congenic spontaneous hypertensive rats (cSHRs) (rats in which piece of chromosome 4 containing wild type Cd36 was integrated into the SHR genome). A bolus infusion of insulin increased iliac conductance and decreased blood pressure in Wistar Kyoto (WKY) rats. However, in SHR insulin did not reduce blood pressure as in WKY but after about 15 min it significantly enhanced blood pressure and reduced iliac conductance. Whereas in cSHR insulin did not reduce blood pressure as in WKY rats. However, pressor responses to insulin were eliminated by chromosome 4 gene transfer. Glucose clearance was significantly slower in both SHR and cSHR. Glucose tolerance test revealed that SHR are hyperinsulinemic and insulin resistant. These findings indicate that transfer of segment of chromosome 4 from Brown Norway rats onto spontaneous hypertensive background eliminates hyperinsulinemia and pressor effects of insulin.
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PMID:Insulin mediated hemodynamic responses in spontaneous hypertensive rats (SHRs): effect of chromosome 4 gene transfer. 1261 24

The objective of this study was to determine the relationships among plasma concentrations of leptin, insulin, and IGF-I with dynamic changes in body condition scores (BCS) in heifers. Nineteen Zebu-Brown Swiss crossbred heifers, 24 to 30 mo old, weighing 322 +/- 9 kg, and with an initial BCS of 2.6 +/- 0.11 (range = 1 to 9) were used. Heifers were fed 60% of their maintenance requirements until they reached a BCS of < or = 2. Heifers were then maintained at that level for 25 d, after which they were fed to gain 1 kg of body weight daily until a BCS of 6 was reached. Heifers were weighed weekly and BCS was measured every 2 wk. Plasma samples were collected twice weekly, and leptin and insulin were determined by RIA. An immunoradiometric assay was used to measure IGF-I from one sample every 2 wk. Plasma concentrations of leptin were positively correlated during nutritional restriction (NR) and weight gain (WG) periods with BCS (r = 0.47 for NR, and r = 0.83 for WG; P < 0.01) and body weight (r = 0.40 for NR, and r = 0.78 for WG; P < 0.01). Plasma concentrations of leptin decreased during nutritional restriction (P < 0.01) as BCS decreased. During weight gain, leptin concentration increased at BCS 3 and thereafter for each integer change in the BCS. Regression analysis showed that changes in body weight affect leptin concentrations within a given BCS. There was a decrease in IGF-I as BCS declined (P < 0.01). During weight gain, by contrast, IGF-I increased significantly (P < 0.01) with every unit change in body condition up to BCS of 4 and plateaued thereafter. Insulin concentrations did not change during nutritional restriction when BCS decreased from 3 to 1. However, once the diet was improved, there was a large increase in insulin concentrations in heifers with BCS 1 (P < 0.01). Among heifers of BCS 2 and 3, insulin did not differ and was lower than in heifers of BCS 1 (P < 0.01). Insulin increased (P < 0.01) among heifers at BCS 4 to 6. Leptin was positively correlated (P < 0.01) with both IGF-I (r = 0.34 for NR, and r = 0.36 for WG) and insulin (r = 0.18 for WG). Insulin was correlated with IGF-I (r = 0.60; P < 0.01). During nutritional restriction, insulin did not correlate with leptin (r = -0.05), BCS (r = -0.03), or IGF-I (r = 0.07). It was concluded that leptin serves as a dynamic indicator of body condition in heifers, as well as an indicator of nutritional status.
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PMID:Plasma concentrations of leptin, insulin-like growth factor-I, and insulin in relation to changes in body condition score in heifers. 1497 42

Genetic studies in human populations and rodent models have identified regions of human chromosome 1q21-25 and rat chromosome 2 showing evidence of significant and replicated linkage to diabetes-related phenotypes. To investigate the relationship between the human and rat diabetes loci, we fine mapped the rat locus Nidd/gk2 linked to hyperinsulinemia in an F2 cross derived from the diabetic (type 2) Goto-Kakizaki (GK) rat and the Brown Norway (BN) control rat, and carried out its genetic and pathophysiological characterization in BN.GK congenic strains. Evidence of glucose intolerance and enhanced insulin secretion in a congenic strain allowed us to localize the underlying diabetes gene(s) in a rat chromosomal interval of approximately 3-6 cM conserved with an 11-Mb region of human 1q21-23. Positional diabetes candidate genes were tested for transcriptional changes between congenics and controls and sequence variations in a panel of inbred rat strains. Congenic strains of the GK rats represent powerful novel models for accurately defining the pathophysiological impact of diabetes gene(s) at the locus Nidd/gk2 and improving functional annotations of diabetes candidates in human 1q21-23.
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PMID:Quantitative trait locus dissection in congenic strains of the Goto-Kakizaki rat identifies a region conserved with diabetes loci in human chromosome 1q. 1526 47

The purpose of this study was to evaluate the effects of insulin on leukocyte-endothelial cell adhesion in the retinal microcirculation in vitro and in vivo. Human retinal endothelial cells (HRECs) were cultured in medium with or without insulin, and neutrophils allowed to adhere. Adherent neutrophils were quantified by measuring myeloperoxidase activity. Surface expression of endothelial adhesion molecules were studied with the use of an enzyme immunoassay. Insulin at concentrations of 50 and 100 microU/ml significantly increased neutrophil adhesion to HRECs compared with the control cells (P < 0.01, respectively). Surface expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased when HRECs were exposed to 100 microU/ml insulin, as compared with the control cells (P < 0.05). Anti-ICAM-1 antibody significantly inhibited neutrophils adhesion to HRECs (P < 0.0001). Brown-Norway rats received subcutaneous injection of 0.2 U per 100 g body weight insulin three times. Control rats received the same amount of phosphate-buffered saline. Leukocyte entrapment in the retina was evaluated using acridine orange leukocyte fluorography. The number of leukocytes trapped in the retina of insulin-treated rats was significantly elevated compared with that in the control animals (P < 0.0001). These results suggested that insulin enhances leukostasis in retinal microcirculation. Hyperinsulinemia may be a risk factor of retinal microcirculatory disturbances.
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PMID:Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1. 1589 55

Currently there is tremendous interest in obesity and its harmful donsequences. Height, weight and body mass index (BMI) along with waist girth are routinely used parameters. One snag in the interpretation of BMI >25 as a measure of obesity is the assumption that the increase is mainly due to fat. This review emphasizes the importance of assessing the muscle component of BMI (by simple somatoscopy or somatotyping). 75 percent of Indian T2DM patients have a normal or low BMI, only 25 percent have BMI >25, wherein muscle mass also contributes as well as fat. Hyperinsulinemia is anabolic to both fat and muscle. Since skeletal muscle is a primary site of insulin resistance, greater the muscle mass, greater the importance of physical exercise to overcome the insulin resistance and greater the importance of dietary supplement of n3-PUFA to optimize the phospholipid composition of the muscle membrane (increasing membrane fluidity and thereby permitting longer residence of GLUT-4 in the plasma membrane). I propose three testable hypotheses: (1) Brown fat (FDG-PET imaging) and UCP2 and UCP3 expression in muscle are positively correlated with ectomorphy and mesomorphy, and negatively correlated with endomorphy and obesity. BAT is absent in obese people. (2) Indian T2DM patients with normal or low BMI have increased UCP2 and UCP3 expession in their muscle, as well as increased high molecular weight adiponectin which promote fatty acid oxidation and prevent obesity. (3) Indian T2DM with BMI >25 and obesity have dysfunction of UCP2 and UCP3. They have high leptin with leptin resistance (induced by hyperinsulinemia) and low adiponectin. There is inverse relationship between adipose mass and adiponectin production.
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PMID:Fat and muscle component of body mass index (BMI): relation with hyperinsulinemia. 1759 32


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