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)

We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin-resistant diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a preclinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer.
 ...
PMID:Autosomal dominant insulin resistance syndrome due to postbinding defect. 128 80

Insulin resistance is seen in several pathophysiological conditions, such as obesity, diabetes mellitus, and essential hypertension. This means that a greater than normal amount of insulin is needed to give a normal biological response. A major biochemical defect in insulin resistance seems to be a defect in the intracellular nonoxidative metabolism of glucose in muscle cells. However, in many individuals, there is also increased hepatic glucose output. The result of insulin resistance in individuals with normal insulin-secreting capacity is hyperinsulinemia, a potential risk factor for cardiovascular disease.
 ...
PMID:Carbohydrate metabolism, insulin resistance, and metabolic cardiovascular syndrome. 128 63

A short review of the metabolic cardiovascular risk syndrome (MCVS) is given. Traditionally, cardiovascular risk has been associated with three so-called "main" risk factors; hypercholesterolemia, hypertension, and smoking. In addition, the association between diabetes and cardiovascular disease has been known for many years in clinical medicine. Primarily, these risk factors have been regarded separately as independent factors, although epidemiological studies showed intercorrelations between them. However, it is now well accepted that relatively few at-risk individuals have only one risk factor, and in many cases a whole "symphony" of factors play together to create what we might call an individuals' risk profile. As an example, very often essential hypertension has been regarded as a disease in itself, which can be successfully treated just by lowering the blood pressure by drugs. When such a strategy obviously failed, the association of elevated blood pressure with dyslipoproteinemia and impaired glucose tolerance attracted more attention, particularly when it was realized that many antihypertensive drugs affected risk in MCVS in a possible negative way. The most important etiologic factor of MCVS is (besides genetics) an excessive caloric intake compared to what the individual spends in physical activity. In the clinical setting, the most important findings of MCVS are central obesity, dyslipoproteinemia with low high-density lipoprotein (HDL) cholesterol, hypertension, reduced insulin sensitivity in peripheral tissues, and increased thrombogenicity. The reduced insulin sensitivity leads to a compensatory increase in beta-cell insulin production, and thereby hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The metabolic cardiovascular syndrome: syndrome X, Reaven's syndrome, insulin resistance syndrome, atherothrombogenic syndrome. 128 71

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
 ...
PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and the majority of the hypertensive population are insulin resistant. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. The initial defect can be directly measured by glucose clamp and other sophisticated techniques; the clinical syndrome may be derived from a network of related variables known to be associated with reduced insulin action. Because neither clamps nor serum insulin screenings will be available on a widespread basis, early diagnosis based on clinical criteria is crucial. A new interpretation of the "thrifty" genotype hypothesis may explain why insulin resistance, which formerly apparently represented an advantage in the evolutionary selection process, is such a frequent phenomenon. Improvement of impaired insulin action as a therapeutic principle may play a future central role in an integrated lifestyle approach of primary prevention of noncommunicable diseases such as NIDDM, hypertension, and atherosclerosis.
 ...
PMID:What is the clinical significance of insulin resistance? 128 40

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.
 ...
PMID:Hypertension and insulin resistance. 128 47

To investigate the hypothesis that insulin resistance plays a role in the etiology of hypertension and hyperlipidemia, we measured serum lipid levels, the fasting glucose/insulin ratio, and the insulin response to oral glucose (GTT) in a group of young obese subjects (n = 21) with hypertension and normal glucose tolerance and in normotensive subjects (n = 36) with normal glucose tolerance, matched for age and body mass index. Leisure time physical activity was evaluated by a questionnaire outlining three levels of physical activities during leisure time. Subjects with hypertension had higher fasting serum insulin (19 +/- 2 v 13 +/- 1 microU/mL, P < .01) and lower fasting glucose/insulin ratio (5.3 +/- 0.2 v 7.1 +/- 0.5 mg/dL/microU/mL, P < .01) than normotensive subjects. Subjects with hypertension had higher peak serum insulin and lower plasma glucose area/insulin area ratio in response to glucose (1.8 +/- 0.2 v 2.4 +/- 0.2 mg/dL/microU/mL, P < .05) than normotensive subjects. Serum total cholesterol, low-density cholesterol, and triglycerides were higher in the obese hypertensive subjects than in obese normotensive ones. Blood pressure correlated with either fasting serum insulin, fasting glucose/insulin ratio, or glucose area/insulin area ratio during GTT. The level of leisure time physical activities was lower in obese hypertensive subjects than in obese normotensive ones. There were significant correlations between the levels of physical activity and the fasting plasma glucose/insulin ratio (r = 0.371, P < .01) or the fasting serum insulin concentration (r = -0.282, P < .05). The study provided evidence that a low level of leisure time physical activity is associated with insulin resistance and resultant hyperinsulinemia, which are the key metabolic abnormalities that link hypertension, obesity, and hyperlipidemia in young subjects.
 ...
PMID:Leisure time physical activity and insulin resistance in young obese students with hypertension. 128 41

The role of insulin and dopamine on blood pressure and renal sodium excretion was evaluated in 10 obese hypertensive patients. Essential hypertensive subjects (age 49.7 +/- 7.7) with at least 26.0kg/m2 obesity were hospitalized and a 2000k cal diet for 7 days (control periods) followed by a 800 k cal for 21 days were given. Salt intake was maintained at 10 g/day throughout this study. Mean blood pressure (MBP), plasma insulin (IRI), urinary dopamine and fractional excretion of sodium (FENa) were measured in both diet periods. Body mass index significantly decreased from 31.6 +/- 4.6kg/m2 to 28.6 +/- 4.1 kg/m2 after weight reduction (P < 0.001). MBP significantly lowered from 112.8 +/- 14.1 mmHg to 100.4 +/- 12.4 mmHg (P < 0.01) and IRI from 9.11 +/- 5.0 microU/ml to 6.3 +/- 5.5 microU/ml (P < 0.001) after weight loss. We observed a significant correlationship between delta MBP and delta IRI (r = 0.754, P < 0.01). Also, we observed a significant correlationship between delta MBP and delta FENa (r = -0.835, P < 0.01). A significant relationship was observed between urinary excretion of sodium and urinary excretion of dopamine (r = 0.507, P < 0.05). We concluded that sodium retention and increase of sympathetic nervous activity by hyperinsulinemia might play an important role of hypertension, and blood pressure reduction by weight loss resulted from decreased insulin and increased excretion of sodium in obesity hypertension.
 ...
PMID:[Effect of weight loss on the reduction of blood pressure in obesity hypertension--hyperinsulinemia and renal sodium retention]. 129 71

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.
 ...
PMID:Hyperinsulinemia, insulin resistance and essential hypertension. 130 12

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


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