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)

Insulin resistance and hyperinsulinemia is now recognized in non-insulin-dependent diabetes, essential hypertension, obesity, atherosclerotic heart disease, dyslipidemia, heart failure, and in heavy smokers. Several mechanisms have been proposed to explain hyperinsulinemia, insulin resistance and its relationship to hypertension; reduced sodium excretion, activation of the sympathetic nervous system, increased activity of the sodium/hydrogen pump, and stimulation of cellular growth. Some of the nonpharmacological methods to control hyperinsulinemia are of benefit in the management of hypertension, most notably weight loss, exercise program, and reduced salt intake. High-fiber and reduced-protein diets also reduce hyperinsulinemia. Thiazide diuretics can result in insulin resistance, and insulin secretion may be inhibited, possibly associated with concomitant hypokalemia. beta-Blockers result in some reduction of glucose tolerance and mask some of the features of hypoglycemia. Angiotensin-converting enzyme (ACE) inhibitors and alpha-receptor blockers do not effect insulin resistance; probably the same is true for calcium antagonists. Although the effect on risk factors should not be discounted, it is the effect of treatment on hard end points, cerebrovascular accidents, myocardial infarction, or death that is most important. Evidence in hypertension is at present restricted to diuretics and beta-blocking drugs.
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PMID:Hypertension and insulin resistance. 128 47

We identified a possible endogenous substrate (pp185) of the insulin-receptor kinase in human adipocytes by treating intact cells with insulin and immunoblotting the cellular extracts with polyclonal antiphosphotyrosine antibody. This 185,000-Mr protein was phosphorylated on tyrosine residues in response to insulin in both rat and human adipocytes. The time course of pp185 phosphorylation at 37 degrees C was rapid and corresponded closely to insulin-receptor autophosphorylation but preceded insulin-stimulated glucose transport. Unlike many growth factor receptors, including the insulin receptor, pp185 was not adsorbed to wheat-germ agglutinin. We found that pp185 phosphorylation occurred at 12 degrees C and that the phosphoprotein was associated with both cytoplasmic and membrane fractions at this temperature. Furthermore, pp185 phosphorylation was induced to the same extent as insulin by vanadate and hydrogen peroxide, compounds previously shown to mimic the biologic effects of insulin. In addition, dose-response analysis of insulin-stimulated glucose transport, receptor autophosphorylation, and pp185 phosphorylation resulted in ED50 values of 0.3, 12, and 12 ng/ml, respectively. These results demonstrate the magnitude of "spare" autophosphorylation and pp185 phosphorylation with respect to glucose transport stimulation in human adipocytes. To determine whether the insulin resistance characteristic of non-insulin-dependent diabetes mellitus (NIDDM) and obesity is associated with a defect in receptor autophosphorylation and/or endogenous substrate phosphorylation, we estimated the extent of beta-subunit and pp185 phosphorylation in adipocytes from NIDDM, obese, and healthy subjects. Although the efficiency of coupling between receptor activation and pp185 phosphorylation was normal in obesity and NIDDM, the capacity for insulin-receptor autophosphorylation was approximately 50% lower in NIDDM subjects compared with nondiabetic obese or lean subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-receptor autophosphorylation and endogenous substrate phosphorylation in human adipocytes from control, obese, and NIDDM subjects. 222 34

In previous studies we found that in healthy subjects, 5 and 10 g of a partially purified amylase inhibitor delayed and decreased starch digestion and reduced postprandial plasma glucose after a starch meal but produced diarrhea in two of six and four of six subjects, respectively. Thus, we wondered whether lower doses of the inhibitor, when given with a meal that contained protein and fat as well as carbohydrate, would have the same effect on carbohydrate tolerance without causing diarrhea. Eight healthy subjects were randomized to receive 2.0 or 2.9 g of the inhibitor with a 650-calorie meal that contained carbohydrate, fat, and protein. In comparison with a placebo, ingestion of 2.9 g, but not 2.0 g, of the inhibitor significantly reduced postprandial increases in plasma glucose (P less than 0.05), C peptide (P less than 0.03), and gastric inhibitory polypeptide (P less than 0.008). Similarly, 2.9 g of the inhibitor in comparison with 2.0 g was associated with more carbohydrate malabsorption and more breath hydrogen excretion. Because the carbohydrate malabsorption observed with the 2.9-g dose was similar to that with the previously tested 5- and 10-g doses of the inhibitor but diarrhea was less frequent, impurities in the partially purified preparation may, in part, have been responsible for these adverse effects. We conclude that 2.9 g of the amylase inhibitor given with a meal that contains a mixture of nutrients is effective in increasing carbohydrate tolerance without causing diarrhea. Therefore, this dose is appropriate for use in studies to determine whether the inhibitor has a beneficial effect in patients with diabetes mellitus or obesity.
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PMID:Effect of a purified amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans. 243 11

A total of 30 patients with alimentary obesity of the I-IV stage, aged from 18 to 40 years, were under study. No diseases of the digestive system were recorded in their anamnesis. Quantitative estimation of intragastric proteolysis (IP) was used for the study of the food action on the gastric secretory function. The protein substrate enclosed into a vinyl chloride tube was introduced into the gastric cavity, then it was removed, and the amount of the digested protein was estimated in micrograms/h. It has been established that the mean level of IP activity in obese patients is significantly higher than in healthy subjects with normal body mass. The investigations conducted have shown that there is a relationship between the IP changes under the action of food and its buffer effect estimated in vitro. The in vitro study of the influence of separate foods on the concentration of hydrogen ions in the acid gastric contents have shown that the buffer effect of the products studied as intensified as follows: tea, bread, milk, meat. The neutralizing effect of a combination of several foodstuffs is determined by the buffer properties of separate products included into the complex.
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PMID:[Data on the buffer effect of food based on the study of intragastric proteolytic activity in patients metabolic-alimentary obesity]. 320 49

The relationship between the resting response to CO2 rebreathing and the ventilatory response to CO2 production during exercise was examined in 20 healthy untrained male subjects and in six patients with obesity hypoventilation syndrome. Patients were chosen because of a severely reduced response to CO2 rebreathing. There was no correlation between the CO2 rebreathing response and the exercise ventilatory response in the normal subjects, the patients, or in the group considered as a whole. This lack of correlation could not be accounted for by differences in ventilatory and occlusion pressure responses nor by reporting responses as a function of a change in hydrogen ion concentration. The independence of the CO2 rebreathing response and the exercise ventilatory response suggests the CO2 rebreathing response does not measure the relevant parameters of ventilatory control during exercise.
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PMID:CO2 rebreathing and exercise ventilatory responses in humans. 642 45

Several previous studies have demonstrated an increased prevalence of gout in New Zealand Maoris. The aetiology of the hyperuricaemia and its effect on morbidity, apart from gout, are unknown. A survey of 115 Maori men of working age revealed a history of gout in 10 (8%) and asymptomatic hyperuricaemia in 26 (23%). The relationship of hyperuricaemia with obesity was confirmed. Alcohol did not make an obvious contribution to the prevalence of hyperuricaemia. Hypertension was more common and creatinine clearance lower amongst those with gout, but not significantly so. The frequency of hypertension and mean creatinine clearance were similar to that seen in asymptomatic hyperuricaemia and normouricaemia. Urate clearance was lower in the gouty and hyperuricaemic subjects. The normouricaemic Maoris had a reduced fractional urate clearance compared with normal men elsewhere. They also excreted a relatively small proportion of hydrogen as ammonium. Both these features are characteristic of gout, and suggest that the Maoris' susceptibility to hyperuricaemia has a renal mechanism. Obesity is common amongst the Maoris and accentuates their natural tendency to hyperuricaemia.
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PMID:Hyperuricaemia, gout and kidney function in New Zealand Maori men. 648 33

Twenty persons living at an altitude of 2,240 meters were studied in order to examine the relative roles of passive and active factors in the genesis of pulmonary arterial hypertension in obesity (overweight, 75 +/- 39 percent). Pulmonary arterial hypertension was present in 80 percent (16) of the patients (mean pulmonary arterial systolic pressure, 45 +/- 17 mm Hg). In 95 percent (19) of the 20 patients, resistance to pulmonary flow at the end of diastole was increased (estimated mean pulmonary arteriolar resistance, 210 +/- 144 dynes.sec.cm-5; mean pulmonary arterial diastolic-pulmonary wedge pressure gradient 7.86 +/- 1.40 mm Hg). The mean arterial oxygen pressure was 50 +/- 9 mm Hg, the arterial carbon dioxide tension was 37 +/- 6 mm Hg and the arterial pH was 7.42 +/- 0.08. Since the pulmonary arterial systolic pressure has been reasonably predicted (r = 0.91; P < 0.001), it would appear that the compliance of the elastic pulmonary arteries in obese patients follows a normal pattern. The behavior of the right ventricular end-diastolic pressure at rest (mean change, 4.6 mm Hg; P < 0.001) and of the pulmonary wedge pressure (mean change, 4.7 mm Hg; P < 0.001) during passive lifting of the legs was indirect evidence of the increase in pulmonary blood volume. The presence of an abnormal resistance to pulmonary blood flow at the end of diastole is suggestive of a decrease in the distention of the pulmonary microcirculation. The pulmonary arterial diastolic-pulmonary wedge pressure gradient and the pulmonary arterial diastolic pressure were related to arterial oxygen unsaturation (r = 0.70; P < 0.05) but not to the concentration of hydrogen ions; thus hypercapnic acidemia appears as a secondary factor in the genesis of pulmonary arterial hypertension at high atitudes. The explanation could be the relative hyperventilation of high altitudes, with a compensatory metabolic alkalosis. The increased pulmonary blood volume and the alveolar hypoxia are the main causes in the pathogenesis of pulmonary arterial hypertension in the grossly obese patient at this altitude.
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PMID:Behavior of the pulmonary circulation in the grossly obese patient. Pathogenesis of pulmonary arterial hypertension at an altitude of 2,240 meters. 741 79

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

Soft drinks containing dietary fiber are popular in Japan. There seem to be two types, one containing polydextrose and the other, oligosaccharide. These beverages are claimed to be useful for constipation or obesity, but data are scanty. We examined four such fiber-containing beverages [Fibe-mini Otsuka Pharmaceuticals (Tokyo, Japan), Seni and Oligo Takeda Food Engineering (Osaka, Japan), Oligo CC (Calpis Food Engineering, Tokyo, Japan), and Sapitus 5289 Nakakita Pharmaceuticals (Nagoga, Japan)] for large intestine fermentability by measuring breath hydrogen (H2) and methane (CH4). Five healthy subjects (two men, three women, 22-48 years old) participated in the study. Breath H2 and CH4 were measured with a MicroLyzer (Quintron Instruments, Milwaukee, Wis.). Breath H2 increased within 2h of beverage consumption, but CH4 excretion was observed in only two subjects. Orocecal transit time was constant for all beverages. Total H2 plus CH4 excretion (AUC; area under the curve) after lactulose was 1294 +/- 250 ppm x min/g fiber. AUC for Oligo CC was significantly greater than that for Fibe-mini or Sapitus 5289 (P < 0.05). The AUCs of Fibe-mini, Seni and Oligo, Oligo CC, and Sapitus 5289 were 41%, 129%, 174%, and 40%, respectively, that of lactulose. It is concluded that commercial fiber-containing drinks produce H2, and CH4 in some people. Oligosaccharide produces more H2 and CH4 than polydextrose.
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PMID:Breath hydrogen and methane excretion produced by commercial beverages containing dietary fiber. 888 30

Amylase inhibition has gastrointestinal and metabolic effects that may aid in the treatment of diabetes and obesity. We tested whether 4 g of a commercially available wheat amylase inhibitor (WAI) affected postprandial carbohydrate (CHO) absorption and plasma glucose or hormones. Twelve persons (four lean and four obese nondiabetics and four obese type II diabetics) were studied on 2 separate days. After eating a weight maintenance diet (55% CHO, 20% protein, and 25% fat, as percentage of calories) for 3 days, subjects ate a breakfast containing 650 kcal, the same proportion of nutrients as calories, and in random order, either WAI or no WAI. Breath H2 and plasma glucose and hormones were measured every 15 and 30 min, respectively, for 7 h. WAI decreased the delta peak postprandial plasma glucose concentrations in 10 of 12 subjects (p < 0.05) and increased the breath H2 levels in 11 (p = 0.02); the increases in breath H2 were small, generally <20 ppm. No subject experienced a change in stools, diarrhea, or bloating. In response to WAI, gastric inhibitory peptide decreased (p < 0.05), peptide YY increased (p < 0.05), and there was a trend toward increased human pancreatic polypeptide (p = 0.07). Although WAI delays CHO absorption and reduces peak postprandial plasma glucose concentrations, overall CHO malabsorption is minimal (as reflected by breath hydrogen and hormones) and without symptoms. It, therefore, may be useful in treating type II diabetes mellitus.
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PMID:Acute postprandial gastrointestinal and metabolic effects of wheat amylase inhibitor (WAI) in normal, obese, and diabetic humans. 970 Sep 50


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