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

The adipocyte membrane G protein pattern, beta-adrenergic receptor activity, and adenylyl cyclase were determined in adipocyte membranes of the db/db mouse, a mutant that is a model of diabetes preceded by hyperinsulinemia, hyperglycemia, and extreme obesity. These studies were undertaken to determine whether the alterations already noted in the ob/ob mouse and those in the db/db mouse are similar and related to the hormonal defects, particularly the hyperinsulinemia and hyperglycemia prevalent in these animals (cf. Ref. 11). The ADP ribosylation data show that Gs alpha was more highly labeled in the tissues of the db/db mutant than in the homozygous control, but there was no significant difference in the amount of ADP-ribose incorporated in the Gi alpha-subunits. Quantification of the proteins by immunodetection revealed that the long (46-kDa) form of Gs alpha was significantly less abundant in the db mutant than in its control, whereas there was no difference in the short (42-kDa) form. Gi alpha-peptides corresponding to Gi alpha 2 and Gi alpha 1 were both less abundant in the db mutant than in the homozygous control. These data contrasted with those obtained for ob mutants and their lean homozygous controls reported previously (4) and confirmed here. It is concluded on the basis of these studies that factors other than the hormonal status are responsible for the G protein patterns in the ob and db mutants. Differences in G protein patterns noted in between the control groups (B/Ks or B/6 homozygotes) correlated strongly with the quantitative differences in adenylyl cyclase response in the two strains.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alpha-subunits of Gs and Gi in adipocyte plasma membranes of genetically diabetic (db/db) mice. 132 37

Changes of platelet aggregation in relation to macroangiopathy and to some of its risk factors were observed in microangiopathy-free, well-controlled type 1 diabetic males. Platelet aggregate ratio was generally lower in patients (n = 77) than in age-matched healthy subjects (n = 48). In the absence of cigarette smoking, hypertension, obesity and hypercholesterolemia (n = 25) in vitro platelet hyperaggregation was found induced with epinephrine, collagen or arachidonic acid, and to a lesser degree with ADP. There was no change in the presence of at least one risk factor in addition to diabetes (n = 29), but there was a further significant increase in platelet aggregation when overt coronary, cerebral or peripheral artery disease was present (n = 23).
 ...
PMID:Platelet function in male diabetics with and without macrovascular complications. 156 30

In human adipocyte plasma membranes, pertussis toxin catalysed the ADP-ribosylation of an apparently single 40 kDa protein. The same protein was also observed in Western blots by using an antibody which identifies the C-terminal decapeptide of Gi alpha (alpha subunit of Gi). In analogous experiments, cholera toxin and an antibody raised against the C-terminal decapeptide of Gs alpha (alpha subunit of Gs) were used to identify two proteins of 42 and 45 kDa, the former of which was more prominent. A method was developed to estimate the relative amounts of Gi and Gs in crude adipocyte plasma membranes in a single immunoblot by using the two antisera. In animal models, changes in the amounts of G-proteins have been suggested to explain alterations in hormone-responsiveness in hypothyroidism and obesity. However, the amounts of Gi and Gs were unaltered in thyroidectomized papillary-carcinoma patients who had been without hormone substitution for 4 weeks. In adipocyte plasma membranes prepared from markedly obese subjects, the amounts of both Gi alpha and Gs alpha as calculated per mg of protein were decreased, but the Gi/Gs ratio remained unaltered in comparison with control subjects.
 ...
PMID:Guanine-nucleotide-binding proteins Gi and Gs in fat-cells from normal, hypothyroid and obese human subjects. 250 51

Seventy-three (58 men and 15 women) survivors of myocardial infarction below 45 years of age and 73 healthy matched controls were investigated regarding in vitro platelet aggregability to ADP and collagen, platelet sensitivity to prostacyclin and plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen. The patients, studied 3-6 months after the acute event, had a reduced platelet sensitivity to prostacyclin. They did not differ from the controls regarding the other platelet function tests. Females had higher platelet reactivity than men. Smoking, obesity or beta-blocker treatment did not influence platelet function. The patients had higher fibrinogen levels than the controls. Gender did not influence, while smoking and obesity increased plasma fibrinogen. Patients on beta-blockade had lower fibrinogen levels than patients without this therapy. The high fibrinogen level and the low platelet sensitivity to prostacyclin might indicate an increased thrombotic liability in young myocardial infarction patients.
 ...
PMID:Platelet function and plasma fibrinogen and their relations to gender, smoking habits, obesity and beta-blocker treatment in young survivors of myocardial infarction. 290 76

The Ivanovas-Sieve (IVA-SIV) rat represents the only available animal model of endogenous hypertriglyceridemia, in the absence of obesity and/or overt diabetes. Since plasma lipids/lipoproteins can modulate platelet reactivity and eicosanoid metabolism, these were examined in two groups of Charles River (CR) and IVA-SIV rats of identical age. The IVA-SIV rats had 2-fold higher plasma triglycerides and a 55% higher number of circulating platelets; the number of platelets was significantly correlated with triglyceridemia. Platelet reactivity to ADP and to collagen was significantly reduced in these animals, whereas the formation of thromboxane B2 did not differ from that of the CR. After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR. Increased levels of the prostacyclin metabolite 6-keto-PGF1 alpha were identified in the perfusate from the aortas of IVA-SIV rats. Platelets from these animals also showed an increased sensitivity to Iloprost, a stable prostacyclin analogue, with an IC50 1.7-fold lower compared to CR rats. Spontaneous hypertriglyceridemia in the IVA-SIV model is not associated with platelet hyperresponsiveness, but rather with a reduced sensitivity to major aggregants.
 ...
PMID:Reduced platelet aggregability and increased vascular prostacyclin formation in a variant rat strain (IVA-SIV) with endogenous hypertriglyceridemia. 321 76

The influence of obesity on myocardial function and metabolism was studied in obese (fa/fa) and thin (Fa/Fa) Zucker rats using the isolated perfused heart as model. Cardiac performance of obese Zucker rats was not impaired. Instead, left ventricular pressure and contractility were increased as compared to controls. In agreement with these findings, creatine phosphate and the ratios of ATP/ADP and creatine phosphate creatine were elevated. The uptake and the conversion of glucose by hearts of obese Zucker rats were impaired. Insulin stimulated the uptake and oxidation of glucose. However, the responsiveness of these processes to insulin was diminished. Lipolysis of endogenous lipids was accelerated severalfold in obesity. Inhibition of fatty acid oxidation by a specific carnitine palmitoyl-transferase inhibitor, phenylalkyloxirane carboxylic acid (POCA), led to a slow rate of lipolysis, and to an acceleration of glucose oxidation and of the basal, noninsulin-dependent uptake of glucose. In the presence of POCA, insulin had, however, no additional stimulatory effect on the glucose uptake by hearts of obese rats. In contrast to hearts of ketotic, acutely diabetic rats where POCA fully restored myocardial responsiveness of glucose uptake and conversion to insulin, in hearts of obese rats only a shift in the glucose pathway from glycolytic formation of lactate and pyruvate to oxidation to CO2 was observed. Thus, POCA can be used as a tool to distinguish different forms of insulin resistance in obesity: 1) a lipid metabolism-dependent defect--presumably an inhibition of phosphofructokinase and pyruvate dehydrogenase by metabolites of fatty acid oxidation, influenced by inhibition of carnitine palmitoyltransferasei, and 2) a lipid metabolism-independent defect in the activation of uptake of glucose and glycogen synthesis by insulin not affected by POCA.
 ...
PMID:Different types of postinsulin receptor defects contribute to insulin resistance in hearts of obese Zucker rats. 373 68

The epidemiological characteristics of platelet aggregability were established in 958 participants in the Northwick Park Heart Study. The main analyses were based on the dose of adenosine diphosphate at which primary aggregation occurred at half its maximum velocity. Aggregability increased with age in both sexes, was greater in whites than blacks (particularly among men), and tended to decrease with the level of habitual alcohol consumption. Aggregability was, however, greater in women than men and in nonsmokers than smokers. There was no relation between aggregability on the one hand and obesity, current or past oral contraceptive use, menopausal state, or blood cholesterol and triglyceride concentrations on the other. Aggregability was somewhat, though not significantly, higher in men with a history of ischaemic heart disease and in those with electrocardiographic evidence of ischaemia than in those without. There was a strong association between the plasma fibrinogen concentration and aggregability. The widely held concept of platelet aggregability and its implications is probably an oversimplification. In the prevention of thrombosis it may be as useful to consider modifying external influences on platelet behaviour, such as plasma fibrinogen concentration or thrombin production, as it is to rely solely on platelet active agents.
 ...
PMID:Epidemiological characteristics of platelet aggregability. 391 15

The platelet aggregation test is not useful for cases of coagulation disorders, and this study attempts to identify the situations in which it cannot provide useful information. This platelet test using the Born aggregometer can be used to identify various pathologies of adhesion, aggregation and ADP, as well as anomalous bleeding. This is not the case for thrombic diseases, because platelets are involved only in arterial thrombosis, and because it is impossible to tell whether or not the platelet anomaly indicated by a positive test was caused by the thrombosis itself. Once activated, platelets become refractory to in vitro stimulation with aggregating agents. The test is thus not specific for hyperaggregation syndromes, and should not be considered as an aid in their study. Data gathered in the Udine territory showed that, in most cases, the platelet aggregation test is required in situations in which it serves no real purpose, especially for women treated with oral contraceptives. In the absence of risk factors such as tobacco smoke, age, diabetes and obesity, oral contraceptives should not be denied based on a positive test, which does not prove that a platelet anomaly exists because of the pill.
 ...
PMID:[Platelet aggregation test. When is it useful?]. 408 Feb 38

This chapter focuses on the biochemical mechanisms that mediate glucose-stimulated insulin secretion (GSIS) from beta-cells of the islets of Langerhans and the potentiating role played by fatty acids. We summarize evidence supporting the idea that glucose metabolism is required for GSIS and that the GLUT-2 facilitated glucose transporter and the glucose phosphorylating enzyme glucokinase play important roles in measuring changes in extracellular glucose concentration. The idea that glucose metabolism is linked to insulin secretion through a sequence of events involving changes in ATP:ADP ratio, inhibition of ATP-sensitive K+ channels, and activation of voltage-gated Ca2+ channels is critically reviewed, and the relative importance of ATP generated from glycolytic versus mitochondrial metabolism is evaluated. We also present the growing concept that an important signal for insulin secretion may reside at the linkage between glucose and lipid metabolism, specifically the generation of the regulatory molecule malonyl CoA that promotes fatty acid esterification and inhibits oxidation. Finally, we show that in contrast to its short term potentiating effect on GSIS, long-term exposure of islets to high levels of fatty acids results in beta-cell dysfunction, suggesting that hyperlipidemia associated with obesity may play a causal role in the diminished GSIS characteristic of non insulin-dependent diabetes mellitus (NIDDM).
 ...
PMID:Metabolic coupling factors in pancreatic beta-cell signal transduction. 757 98

To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjects and nine age-matched healthy volunteers and from eight NIDDM obese patients and nine age-matched healthy volunteers after a 3-min incubation with human recombinant insulin (0, 240, 480, 960, and 1,920 pmol/l). Platelet aggregation was evaluated using different ADP doses to measure the ADP concentration determined on the basis of a dose-response curve necessary to elicit a maximal aggregation of 50% (ED50). Insulin induced a dose-dependent decrease of platelet aggregation to ADP (P = 0.0001) in healthy subjects. A significant effect was evident starting from an insulin concentration of 240 pmol/l. On the contrary, in insulin-resistant subjects, insulin reduced platelet sensitivity to ADP only at a concentration of 1,920 pmol/l. When ADP ED50 values obtained in platelet-rich plasma incubated with insulin were expressed in percentage of the ADP ED50 values obtained in platelet-rich plasma without insulin, considered as 100%, we observed that ADP ED50 with 1,920 pmol/l insulin was 153.6 +/- 13.2% in the younger healthy subject group (P = 0.004), 150.0 +/- 3.8% in the older healthy subject group (P = 0.0001), 116.1 +/- 6.1% in obese subjects (P = 0.031), and 120.0 +/- 8.6% in NIDDM patients (P = 0.05). In healthy subjects, insulin induced a dose-dependent increase of platelet cGMP (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients. 758 30


1 2 3 4 5 6 7 8 9 10 Next >>