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

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
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PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

1. The gene for dipeptidyl carboxypeptidase 1 (angiotensin I-converting enzyme, kininase II; DCP1), located on chromosome 17q23, has been implicated in hypertension in rats. In humans associations have been found for the insertion allele of a bi-allelic insertion/deletion polymorphism of DCP1 with hypertension and the deletion allele with myocardial infarction. Other hypertension studies have, however, failed to find a relationship. 2. Mathematical predictions based on DCP1 association data suggest that high sib-pair numbers may be needed to achieve statistical significance by this approach, although differences in the severity of hypertension in different study groups could account for the disparate findings. 3. No association was found between DCP1 allele or genotype frequencies and obesity in essential hypertensives.
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PMID:Chromosome 17q23: a locus for cardiovascular disease. 839 42

Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole-body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.
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PMID:Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism. 852 93

Angiotensin II regulates blood pressure and may affect adipogenesis and adipocyte metabolism. Angiotensin II is produced by cleavage of angiotensinogen by renin and angiotensin-converting enzyme in the circulation. In addition, angiotensin II may be produced in various tissues by enzymes of the renin-angiotensin system (RAS) or the nonrenin-angiotensin system (NRAS). We have analyzed the expression of angiotensinogen and enzymes required for its conversion to angiotensin II in human adipose tissue. Northern blot demonstrated angiotensinogen expression in adipose tissue from nine obese subjects. Western blot revealed a distinct band of expected size of the angiotensinogen protein (61 kDa) in isolated adipocytes. RT-PCR, followed by Southern blot, demonstrated renin expression in human adipose tissue. Angiotensin-converting enzyme messenger RNA was detected by RT-PCR, and the identity of the PCR products was verified by restriction enzyme cleavage. Transcripts for cathepsin D and cathepsin G, components of the NRAS, were detected by RT-PCR, verified by restriction enzyme cleavage. We conclude that human adipose tissue expresses angiotensinogen and enzymes of RAS and NRAS. This opens the possibility that angiotensinogen-derived peptides, produced in adipose tissue itself, may affect adipogenesis and play a role in the pathogenesis of obesity.
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PMID:Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. 981 70

The enzyme 11 beta HSD catalyzes the interconversion of the biologically active cortisol and the biologically inactive cortisone. There are two distinct isozymes: 11 beta HSD type 1 is mainly expressed in liver and is a bidirectional enzyme, with both dehydrogenase and reductase activity. 11 beta HSD type 2 is mainly expressed in kidney and is a unidirectional enzyme with only dehydrogenase activity. 11 beta HSD type 2 protects the mineralocorticoid receptor from being activated by cortisol. Thus, specificity of this receptor in vivo is enzyme and not receptor mediated. The syndrome of apparent mineralocorticoid excess is caused by a congenital deficiency of 11 beta HSD type 2. Liquorice-induced hypertension is an example of an acquired defect in dehydrogenase activity of 11 beta HSD, caused by glycyrrhetinic acid. 11 beta HSD may play a role in the pathogenesis of 'essential' hypertension, obesity and type 1 diabetes mellitus. Angiotensin-converting enzyme inhibitors enhance dehydrogenase activity of 11 beta HSD, which may contribute to their natriuretic effect.
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PMID:[11 beta-hydroxysteroid-dehydrogenase: characteristics and the clinical significance of a key enzyme in cortisol metabolism]. 1032 Dec 59

The association of obesity and hypertension is characterized hemodynamically by an increase in absolute circulating intravascular volume that induces increased cardiac output and total peripheral resistance that remains inappropriately normal. These changes constitute the hemodynamic basis for the increase in blood pressure in obesity. Obesity-associated hypertension is also characterized by an abnormal renal response, including increased renal blood flow and a rise in glomerular and interstitial pressures. These hemodynamic changes induce the following structural changes in the heart: enlarged left atrial, ventricular and aortic root diameters as well as increased posterior septal wall thickness and left ventricular mass. The hemodynamic changes in the kidneys generate higher glomerular volume and increased interstitial infiltrate, which may cause compression of the tubules and blood vessels of the renal medulla. Weight reduction is an effective tool in the control of blood pressure, and significantly reduces the metabolic and hemodynamic derangements that occur with obesity. However, since weight reduction compliance is difficult to maintain, pharmacological agents are often needed to control blood pressure. Angiotensin-converting enzyme inhibitors, calcium channel blockers and alpha- adrenergic blocking agents may be the most appropriate therapy for obesity-associated hypertension since they intervene with some of the previously described pathophysiological conditions.
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PMID:Obesity-associated hypertension: hypothesized link between etiology and selection of therapy. 1082 14

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.
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PMID:Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial. 1084 69

Diabetic nephropathy (DN) is the number one cause of end-stage renal disease in United States and is highly prevalent in African Americans. We have found that among African Americans in Mississippi diabetic nephropathy appears to affect females more than males, which may be related to increased rates of obesity and diabetes in African American women. Glycemic control and control of blood pressure is essential to prolong renal survival and to protect against cardiovascular events. Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality in diabetics and are tolerated in advanced renal disease. The impact of glycemic control, appropriate antihypertensives, and the optimal level of blood pressure control in African Americans with advanced DN require further study. This article reviews the impact, clinical characteristics, risk factors, and treatment of diabetic nephropathy in African Americans.
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PMID:Diabetic nephropathy in African Americans. 1141 48

Insulin resistance and/or compensatory hyperinsulinemia are associated with hypertension, obesity, dyslipidemia, and glucose intolerance. Insulin resistance and hyperinsulinemia are considered to increase blood pressure through sympathetic nervous system activation, renin-angiotensin system stimulation, and vascular smooth muscle cell proliferation. Leptin, magnesium ions, nitric oxide, endothelin, peroxisome proliferator-activated receptor gamma, and tumor necrosis factor-alpha also modulate blood pressure. Decreasing insulin resistance by lifestyle modification including diet, weight loss, and physical exercise has been shown to reduce blood pressure. Angiotensin-converting enzyme inhibitors have a beneficial effect on insulin resistance. On the other hand, the angiotensin II antagonist, losartan, does not affect insulin sensitivity. The selective alpha1-blockers have a favorable metabolic profile producing increases in insulin sensitivity. A short-acting type calcium channel blocker seems to decrease insulin sensitivity. On the other hand, long-acting type calcium channel blockers improve insulin sensitivity. Thiazide diuretics and most of the beta-blockers decrease insulin sensitivity. Vasodilatory beta-blockers have been reported to improve insulin sensitivity. Use of low-dose diuretics avoids the adverse effects seen with conventional doses.
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PMID:Hypertension and insulin disorders. 1241 78


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