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)

Obesity, especially visceral adiposity, is a major determinant of the development of type 2 diabetes. Both visceral adiposity and insulin resistance are strongly related to cardiovascular risk factors in diabetic and non-diabetic subjects. One of the areas where the correlation between visceral fat (upper body adiposity) and cardiovascular risk is most apparent is the prediabetic state. We have recently shown that only prediabetic subjects (those who later develop type 2 diabetes) who are insulin resistant and with upper body adiposity have increased triglycerides, decreased HDL cholesterol and high blood pressure.
 ...
PMID:Obesity and the metabolic syndrome: the San Antonio Heart Study. 1088 94

Sand rats develop obesity, insulin-resistance, hyperlipidemia and prediabetes, when given a standard laboratory chow diet. We have used this model to demonstrate the beneficial action of olea europea var. oleaster leaves to regulate unbalanced metabolism. 32 sand rats fed on hypercaloric diet during 7 months, were divided into 3 groups: controls (n=10), treated by plant (n=13) and treated by simvastatin (Zoco); hypocholesterolemic drug. The plant decoction prepared at 10% was given orally at the rate of 1.5 ml/100g during 3 months. Results show that the plant presents a hypocholesterolemic effect (42%) related to decreases in LDL and VLDL cholesterol. In addition, hypoglycemic (16%) and antihyperglycemic (40%) effects were observed accompanied by a 27% decrease in insulin. Chronic treatment with Zocor reduced total cholesterol (32%), LDL and VLDL cholesterol. Both of treatments produced no significantly reduction in plasma levels of triglycerides and HDL cholesterol. No noxions effect of this plant have been observed in usual doses.
 ...
PMID:[Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and lipid metabolism in obese and prediabetic sand rats (Psammomys obesus)]. 1091 76

In pancreatic beta-cells, glucose metabolism signals insulin secretion by altering the cellular array of messenger molecules. ATP is particularly important, given its role in regulating cation channel activity, exocytosis, and events dependent upon its hydrolysis. Uncoupling protein (UCP)-2 is proposed to catalyze a mitochondrial inner-membrane H(+) leak that bypasses ATP synthase, thereby reducing cellular ATP content. Previously, we showed that overexpression of UCP-2 suppressed glucose-stimulated insulin secretion (GSIS) in isolated islets (1). The aim of this study was to identify downstream consequences of UCP-2 overexpression and to determine whether insufficient insulin secretion in a diabetic model was correlated with increased endogenous UCP-2 expression. In isolated islets from normal rats, the degree to which GSIS was suppressed was inversely correlated with the amount of UCP-2 expression induced. Depolarizing the islets with KCl or inhibiting ATP-dependent K(+) (K(ATP)) channels with glybenclamide elicited similar insulin secretion in control and UCP-2-overexpressing islets. The glucose-stimulated mitochondrial membrane ((m)) hyperpolarization was reduced in beta-cells overexpressing UCP-2. ATP content of UCP-2-induced islets was reduced by 50%, and there was no change in the efflux of Rb(+) at high versus low glucose concentrations, suggesting that low ATP led to reduced glucose-induced depolarization, thereby causing reduced insulin secretion. Sprague-Dawley rats fed a diet with 40% fat for 3 weeks were glucose intolerant, and in vitro insulin secretion at high glucose was only increased 8.5-fold over basal, compared with 28-fold in control rats. Islet UCP-2 mRNA expression was increased twofold. These studies provide further strong evidence that UCP-2 is an important negative regulator of beta-cell insulin secretion and demonstrate that reduced (m) and increased activity of K(ATP) channels are mechanisms by which UCP-2-mediated effects are mediated. These studies also raise the possibility that a pathological upregulation of UCP-2 expression in the prediabetic state could contribute to the loss of glucose responsiveness observed in obesity-related type 2 diabetes in humans.
 ...
PMID:Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. 1137 30

Although both maternal obesity and diabetes mellitus increase the risk for neural tube defects, it is unknown whether they are independent risk factors or manifestations of an underlying prediabetic state such as hyperinsulinemia. We investigated whether hyperinsulinemia was a risk factor for neural tube defects independent of obesity and hyperglycemia in Mexican-American women. We identified case and control women from residents delivering or terminating pregnancies in hospitals or birthing centers in any of the 14 Texas-Mexico border counties during 1995-2000. Case women had a pregnancy affected by anencephaly, spina bifida, or encephalocele; randomly selected control women had normal births, frequency matched by year and birth facility. Questionnaire and laboratory values obtained 5-6 weeks postpartum were available for 149 case and 178 control women. Both hyperinsulinemia and obesity were related to increased neural tube defect risk [odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.01 and OR = 1.73, 95% CI = 1.03-2.92, respectively]. Adjustment for obesity only slightly reduced the effect of hyperinsulinemia (OR = 1.75, 95% CI = 1.09-2.82). Alternatively, a modest effect remained for obesity after adjustment for hyperinsulinemia (OR = 1.45, 95% CI = 0.84-2.51). Hyperinsulinemia is a strong risk factor for neural tube defects and may be the driving force for the observed risk in obese women.
 ...
PMID:Effects of hyperinsulinemia and obesity on risk of neural tube defects among Mexican Americans. 1167 89

The prevalence of diabetes in Spain is about 6% and increases with age and obesity. Diabetes is present in approximately 25% of patients with coronary heart disease (CHD). Pre-diabetic and diabetic patients have a higher incidence of CHD and poorer prognosis, with high short- and long-term mortality. The protective effect of pre-menopause status is suppressed by diabetes. Diabetes has a synergic effect with other cardiovascular risk factors. Primary prevention in diabetic patients should be approached as in non-diabetic post-infarction patients. In diabetes, a healthy life-style and strict control of blood sugar and the other cardiovascular risk factors, particularly hypertension, is mandatory.
 ...
PMID:[Prognosis of diabetic patients with ischemic cardiopathy]. 1211 3

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.
 ...
PMID:Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. 1246 45

Type 2 diabetes is the most common form of hyperglycemia. The disease exists in all populations, but in developed societies, the prevalence has risen as the population ages and above all becomes more obese. In the prediabetic state, type 2 diabetes involves two defects, peripheral insulin resistance and hyperinsulinemia, which is followed by the failure of insulin secretion to compensate for the insulin resistance. As with nearly any disease, it is likely that multiple environmental and genetic factors are involved in the development of insulin resistance. An acquired pathogenic factor is obesity, particularly visceral obesity. Compelling evidence suggests that progressive dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, with elevated levels of circulating cortisol, is implicated in the development of visceral obesity. The HPA axis perturbations associated with visceral obesity can be accounted for, in part, by increased environmental stress that destabilizes the hypothalamic-pituitary system in individuals with genetic susceptibility.
 ...
PMID:Stress induced disturbances of the HPA axis: a pathway to Type 2 diabetes? 1260 4

The high prevalence of insulin resistance syndrome in African Americans predisposes this population to higher morbidity and mortality from cardiovascular disease. To test the hypothesis that the combination of obesity and high blood pressure (BP) represents the physical phenotype of insulin resistance syndrome, 337 African-American men and women aged 32+/-4 years were examined and classified into four groups (nonobese-normal BP, nonobese-high BP, obese-normal BP, obese-high BP), according to presence or absence of obesity and high BP. Mean values of glucose, insulin, lipids, urinary albumin excretion, and clamp-derived insulin sensitivity were determined for each group. Prevalence of prediabetes (24.4%), diabetes (19.2%), and insulin resistance syndrome (87.2%) were highest in the obese-high BP group (p<0.001). Mean triglycerides, urinary albumin excretion, fasting glucose, fasting insulin, and insulin resistance were highest in the obese-high BP group (p<0.001). Subjects with both obesity and high BP showed greater expression of lipid and glucose abnormalities, higher urinary albumin excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and insulin resistance syndrome.
 ...
PMID:Obesity and high blood pressure: a clinical phenotype for the insulin resistance syndrome in African Americans. 1524 91

The peptidic neurotransmitter neuropeptide Y (NPY) has been functionally implicated in feeding behavior, cardiovascular regulation, control of neuroendocrine axes, affective disorders, seizures, and memory retention. At least five different receptors mediate NPY actions. In particular, the Y1 receptor appears to be involved in a variety of NPY-induced pathways. This review summarizes the main findings resulting from the use of mice lacking NPY Y1 receptor expression. Interestingly, the overall phenotype of Y1 knockouts mimics metabolic syndrome, which is characterized by obesity, a prediabetic state, and a susceptibility to develop hypertension.
 ...
PMID:Importance of NPY Y1 receptor-mediated pathways: assessment using NPY Y1 receptor knockouts. 1533 79

Hyperleptinemia, associated with prediabetes, is an independent risk factor for coronary artery disease and a mediator of coronary endothelial dysfunction. We previously demonstrated that acutely raising the leptin concentration to levels comparable with those observed in human obesity significantly attenuates coronary dilation/relaxation to acetylcholine (ACh) both in vivo in anesthetized dogs and in vitro in isolated canine coronary rings. Accordingly, the purpose of this investigation was to extend these studies to a model of prediabetes with chronic hyperleptinemia. In the present investigation, experiments were conducted on control and high-fat-fed dogs. High-fat feeding caused a significant increase (131%) in plasma leptin concentration. Furthermore, in high-fat-fed dogs, exogenous leptin did not significantly alter vascular responses to ACh in vivo or in vitro. Coronary vasodilator responses to ACh (0.3-30.0 microg/min) and sodium nitroprusside (1.0-100.0 microg/min) were not significantly different from those observed in control dogs. Also, high-fat feeding did not induce a switch to an endothelium-derived hyperpolarizing factor as a major mediator of muscarinic coronary vasodilation, because dilation to ACh was abolished by combined pretreatment with N(omega)-nitro-l-arginine methyl ester (150 microg/min ic) and indomethacin (10 mg/kg iv). Quantitative, real-time PCR revealed no significant difference in coronary artery leptin receptor gene expression between control and high-fat-fed dogs. In conclusion, high-fat feeding induces resistance to the coronary vascular effects of leptin, and this represents an early protective adaptation against endothelial dysfunction. The resistance is not due to altered endothelium-dependent or -independent coronary dilation, increased endothelium-derived hyperpolarizing factor, or changes in coronary leptin receptor mRNA levels.
 ...
PMID:Leptin resistance extends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction. 1589 77


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