Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

D-glucose was previously reported to cause a concentration-related decrease in the 36Cl- content of prelabeled islets prepared from ob/ob mice, a current animal model of inherited obesity. From these findings, it was inferred that the hexose stimulates Cl- efflux from islet cells and that such an increase in Cl- permeability may partly mediate glucose-induced depolarization of insulin-producing cells. The aim of the present study was to investigate the possible extension of these findings to islets prepared from normal rats by measuring the changes evoked by increasing concentrations of D-glucose in 36Cl- outflow itself from prelabeled isolated islets. After 60 min preincubation at 37 degrees C in the presence of 3 mM D-glucose and 36Cl- (75 microCi/mL), the islets were incubated for 8-10 min at 37 degrees C in the presence of increasing concentrations of the hexose (3-20 mM). The changes in 36Cl- outflow during incubation indicated that D-glucose, in excess of a threshold concentration close to 5 mM, indeed increases effluent radioactivity from the prelabeled islets. It is proposed, therefore, that a gating of volume-sensitive anion channels in glucose-stimulated insulin-producing islet cells participates in the depolarization of the plasma membrane recorded in the range of insulinotropic concentrations of the hexose.
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PMID:Stimulation by D-glucose of 36Cl- efflux from prelabeled rat pancreatic islets. 1554 2

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and adipocyte gene expression in adipocytes. In this study, we have shown for the first time the gene expression profile in isolated rat adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The rat adipocytes were treated with 100 muM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. A total of 633 or 427 genes was up-regulated (>1.5-fold) by the treatment of adipocytes with C3G or Cy, respectively. The up-regulated genes include lipid metabolism and signal transduction-related genes, however, the altered genes were partly different between the C3G- and Cy-treated groups. Based on the gene expression profile, we demonstrated the up-regulation of hormone sensitive lipase and enhancement of the lipolytic activity by the treatment of adipocytes with C3G or Cy. These data have provided an overview of the gene expression profiles in adipocytes treated with anthocyanins and identified new responsive genes with potentially important functions in adipocytes related with obesity and diabetes that merit further investigation.
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PMID:Gene expression profile of isolated rat adipocytes treated with anthocyanins. 1586 61

The present study was conducted to assess whether glucagon-like peptide-1 (GLP-1) release and appetite after a breakfast with or without an additional galactose/guar gum stimulation is different in normal-weight compared with overweight/obese subjects. Twenty-eight overweight/obese (BMI 30.3 (sd 2.7) kg/m2; age 44.3 (sd 9.7) years) and thirty normal-weight subjects (BMI 22.8 (sd 1.4), age 31.5 (sd12.8) years) participated in a crossover study. Fasting and postprandial plasma GLP-1, insulin, glucose and free fatty acid concentrations were measured in response to either a galactose (50 g)/guar gum (2.5 g) load (836 kJ) and a standard breakfast (1.9 MJ; GG), or water (250 ml) and the standard breakfast (W) every 30 min relative to the ingestion for 120 min. Appetite was assessed using 100 mm visual analogue scales. GLP-1 concentrations were significantly increased after GG at 30 and 60 min compared with W in both groups. Plasma GLP-1 concentrations in the W condition were higher in normal-weight than overweight/obese subjects (P=0.03). No difference was observed in the GG condition between groups. Satiety was increased in normal-weight compared with overweight/obese subjects in the GG condition at 30 (P=0.02) and 60 (P=0.04) min. We conclude that after a standard breakfast with water, GLP-1 release was lower in the overweight/obese than the normal-weight subjects. However, postprandial GLP-1 release in overweight/obese subjects was no different from that of normal-weight subjects when galactose/guar gum was added to the breakfast. The latter was not mirrored by subjective feelings of satiety. Disturbed perception of the physiological feedback of a satiety hormone rather than disturbed feedback itself might contribute to obesity.
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PMID:Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects. 1602 53

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.
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PMID:A causal role for uric acid in fructose-induced metabolic syndrome. 1623 13

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients 'at risk' of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.
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PMID:Hyperglycemic hyperosmolar nonketotic syndrome. 1644 62

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and its gene expression in adipocytes. In this study, we have shown the gene expression profile in human adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The human adipocytes were treated with 100 microM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. Based on the gene expression profile, we demonstrated the significant changes of adipocytokine expression (up-regulation of adiponectin and down-regulation of plasminogen activator inhibitor-1 and interleukin-6). Some of lipid metabolism related genes (uncoupling protein2, acylCoA oxidase1 and perilipin) also significantly induced in both common the C3G or Cy treatment groups. These studies have provided an overview of the gene expression profiles in human adipocytes treated with anthocyanins and demonstrated that anthocyanins can regulate adipocytokine gene expression to ameliorate adipocyte function related with obesity and diabetes that merit further investigation.
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PMID:Microarray profiling of gene expression in human adipocytes in response to anthocyanins. 1648 47

GLP-1 has anorectic properties and regulates fuel homeostasis through both its insulinotropic and insulinotrophic actions and effects in extrapancreatic tissue. This study is aimed at characterizing the response to GLP-1 of adipocytes from obese patients, in terms of D-glucose transport and lipid metabolism, in comparison with data from normal subjects. Adipocytes were obtained by enzymatic digestion from the abdominal fat tissue of 25 morbidly obese patients and 8 normal subjects undergoing bariatric or inguinal hernia surgery, respectively. Basal GLUT4 expression, D-glucose transport, glycerol release and lipogenesis were measured in cells treated, when required, with 10(-12)-10(-9) M GLP-1, insulin, glucagon and the GLP-1 structurally related peptides, exendin-4 and exendin-9. In obese patients, versus normal subjects, a trend towards lower values was found in GLUT4 protein or mRNA, although the differences were not statistically significant; insulin-stimulated glucose uptake was higher and cells did not respond to GLP-1, while both exendins (10(-10) and 10(-9) M) exerted an inhibitory action; basal lipolysis was higher and so was the effect of GLP-1 and glucagon, whereas insulin abolished the lipolytic action of all peptides; both basal lipogenesis and the response to insulin were higher while GLP-1 and exendin-4 were ineffective. These results document the analogies and dissimilarities between the response to GLP-1, exendin-4 and exendin-9, as well as to insulin and glucagon, relative to glucose transport and lipid metabolism of fat tissue from obese patients versus normal subjects, the reduced lipogenic effect and enhanced lipolytic action of GLP-1 being, perhaps, adequate for its therapeutic use in obesity.
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PMID:Effect of GLP-1 on D-glucose transport, lipolysis and lipogenesis in adipocytes of obese subjects. 1668 26

Immunocompromised hematopoietic stem cell transplant (HSCT) recipients frequently receive total parenteral nutrition (TPN), a dextrose-based solution that may exacerbate the infectious risks associated with hyperglycemia. This study assessed the incidence of hyperglycemia (glucose level>or=110 mg/dL) and its effect on clinical outcomes in TPN versus non-TPN recipients who received HSCTs. A retrospective cohort of 357 adults who were admitted for initial autologous or allogeneic transplantation at 2 university-affiliated centers was examined. To discern the temporality of outcomes, "before" and "after" comparisons were made by using actual infusion times for TPN patients and using timeframes based on mean hospital days before ("before") or during ("after") parenteral infusion for non-TPN patients. Patients demonstrated similar demographic and clinical characteristics when analyzed by institution, feeding, and donor-type strata, and 57% received TPN. After attempts to equilibrate disease acuity were employed, the proportion of hyperglycemic days was equivalent before but significantly greater after in patients exposed versus unexposed to TPN (87.5% versus 8.3%, respectively; P<.001). Using logistic regression, the likelihood of infection doubled (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.4-3.5) after adjustment for donor type, diagnosis, age, gender, ethnicity, institution, mucositis, and obesity. This association was only slightly attenuated when patients with infections before were removed (OR, 1.9; 95%, CI, 1.1-3.3), steroid recipients were eliminated (OR, 2.1; 95% CI, 1.2-3.4), and when patients with nonablative regimens were excluded (OR, 2.1; 95% CI, 1.3-3.5), but was considerably higher for patients who were classified as normal or underweight (body mass index<or=25 kg/m2; n=118; OR, 4.3; 95% CI, 1.7-10.6). In addition, the effect of TPN became insignificant when glucose was added as an independent variable, thus symbolizing their collinear relation. Parenteral nutrition recipients versus nonrecipients also developed significantly greater requirements for red cell (P=.001) and platelet transfusions (P=.001) after and significant delays in granulocyte and platelet engraftment times for autologous (P=.01) and allogeneic (P=.02) subjects. The broad use of TPN in patients undergoing initial HSCT was associated with profound hyperglycemia, resultant greater morbidity, and questionable efficacy in this adult, well-nourished cohort.
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PMID:Adverse clinical consequences of hyperglycemia from total parenteral nutrition exposure during hematopoietic stem cell transplantation. 1673 39

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.
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PMID:Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry. 1702 42

We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin [corrected]. IC50s for quercetin, myricetin, and isoquercitirin [corrected]were approximately 200- to 1000-fold less than glucose or fructose concentrations, and noncompetitive inhibition was observed. The two other major intestinal sugar transporters, GLUT5 and SGLT1, were unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco-2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco-2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters. Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic.
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PMID:Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. 1717 39


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