Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Young Obese/SHR, genetically destined to become obese were made to run three times daily, averaging 2740 ft/day. Siblings of these young Obese/SHR which were allowed to remain sedentary, developed voracious appetites, massive obesity, hyperlipidemia, diabetes, hypertension, hyperadrenocorticism, muscle wasting, kidney stones, thin skin, and accelerated aging. The Obese/SHR that exercised did not become obese, their blood lipid, glucose, BUN, blood pressure, and hyperadrenocorticism were reduced, but their testes and ovaries became prematurely atrophic.
 ...
PMID:Jogging reduces obesity and hypertension in obese/SHR. 631 Jun 22

We used primary cultures of rat hepatocytes to evaluate the effects of glucocorticoids on insulin-responsive hepatic lipogenesis. The data indicate that hepatocytes incubated for 20 h with dexamethasone (0.1 microM) alone are profoundly resistant to the ability of insulin to stimulate lipogenesis acutely. In contrast, primary cultures of hepatocytes incubated with dexamethasone plus insulin are hyper-responsive to the ability of insulin to stimulate lipogenesis chronically. This potentiation of insulin action by a glucocorticoid occurs at physiological concentrations of the two hormones. Exposure to dexamethasone plus insulin for more than 4 h is required for the two hormones to enhance insulin action either by overcoming the insulin resistance induced by dexamethasone alone or by stimulating insulin action induced by insulin alone. Despite the marked potentiation of insulin action, hepatocytes exposed to dexamethasone plus insulin are less sensitive to insulin, as demonstrated by a shift to the right in the dose-response curve for insulin-stimulated lipogenesis. The resistance of hepatocytes to the acute effects of insulin after exposure to dexamethasone alone and the potentiation of insulin action and decreased sensitivity to insulin after exposure to insulin plus dexamethasone are all mediated by post-insulin-binding events. These studies demonstrate potentiation of insulin action in the liver by physiological concentrations of glucocorticoids and may have physiological significance for the regulation of normal hepatic lipogenesis, for the hyperlipidaemia observed with the pharmacological use of glucocorticoids, and for disease states in man associated with hyperinsulinaemia and hypercortisolism.
 ...
PMID:The effects of glucocorticoids on insulin-stimulated lipogenesis in primary cultures of rat hepatocytes. 634 91

Male, 5 months old, massively obese, spontaneously hypertensive rats (Obese/SHR) were given 10 mg alloxan/100 g b.w., s.c., to induce diabetes. Control Obese and non-obese/SHR were given saline. Insulin therapy was withheld. All of the animals were killed at 6 months of age. Alloxan caused a slight but statistically significant increase in blood pressure, pituitary and adrenal glandular hyperplasia, hyperlipidemia, hyperglycemia, and increased BUN levels. The giant sized islets of Langerhans in Obese/SHR showed only partial degranulation of the insulin-producing beta cells concomitant with residual but apparently adequate blood insulin levels, whereas the islets of non-obese/SHR exhibited virtually total beta cell degranulation and only trace amounts of blood insulin. The alloxanized, non-obese rats were severely emaciated; the alloxanized Obese/SHR maintained their obesity. Alloxan-treated, Obese and non-obese/SHR manifested gross and microscopic degenerative changes suggesting acceleration of the normal aging process. The genetically-programmed pathogenesis of diabetes, obesity, hypertension, and Cushingoid pathophysiology of Obese/SHR may be due to hyperadrenocorticism.
 ...
PMID:Resistance of obese and non-obese, spontaneously hypertensive rats to alloxan-induced diabetes. 635 Jul 80

Male and female, massively obese and nonobese, spontaneously hypertensive rat (SHR) which are hypersensitive to stress were kept under quiescent conditions; they were autopsied at 15 months of age. The blood pressure of the Obese/SHR plateaued at 166 mmHg versus 198 mmHg for the nonobese/SHR. The once massive thymi vanished in the Obese/SHR accompanied by greatly enlarged adrenal glands, pituitary basophilia, greatly elevated levels of adrenocorticotrophin, corticosterone, deoxycorticosterone, aldosterone, fatty liver, hyperlipidemia, and hyperglycemia. The Obese/SHR were hyperadrenocorticoid compared with their nonobese siblings and manifested a Cushingoid spectrum of degenerative changes (e.g., thin skin, hypertension, diabetes, kidney stones, and accelerated aging). The provision of a nonstressful environment is believed to have dampened the usual chronic hyperadrenocorticism and prolonged the lifespan of the Obese/SHR.
 ...
PMID:Cushingoid pathophysiology of old, massively obese, spontaneously hypertensive rats (SHR). 682 32

Lipid metabolism was studied in 21 horses with hyperadrenocorticism. To be included in the study, horses had to have histologic evidence of a pars intermedia adenoma found at necropsy (n = 9), a baseline ACTH concentration greater than 400 pg/ml (n = 6), or a plasma cortisol concentration 2 hours after i.v. administration of 25 IU of ACTH greater than 413 nmol/L (n = 16). Mean +/- SD baseline plasma cortisol concentration was 338 +/- 261 nmol/L (n = 20), mean +/- SD plasma insulin concentration was 97 +/- 54 microU/ml (n = 15), mean +/- SD plasma beta-hydroxybutyrate concentration was 1.8 +/- 1.2 mg/dl (n = 21), and mean +/- SD plasma nonesterified fatty acids concentration was 6.2 +/- 6.4 mg/dl (n = 21). None of the horses had hyperlipemia. Compared with clinically normal horses, horses with hyperadrenocorticism had increased lipolysis and increased ketogenesis. It was concluded that cortisol cannot be the sole factor contributing to insulin resistance in horses with hyperadrenocorticism.
 ...
PMID:Lipid metabolism in horses with hyperadrenocorticism. 776 7

Obesity is a multifactorial heterogenous condition. The location of excess fat on the body determines the risk of morbidity and mortality for significant disease. Visceral, or intraabdominal, fat is the fat depot most highly associated with illness and death from cardiocerebrovascular disease and diabetes. Visceral fat is also associated with a quartet of metabolic disturbances. Referred to as the metabolic syndrome, these abnormalities include hypertension, hyperlipidemia, hyperinsulinemia, and insulin resistance. The metabolic syndrome is also present in Cushing's syndrome, which is characterized by primary hypercortisolism as well as profound visceral adiposity and obesity. The interrelationship between hyperactivation or hypersensitivity of the stress axis and disease can be elucidated by an understanding of the effect of excess glucocorticoids upon energy storage and metabolism. The complex interactions of the stress axis upon the growth and reproductive axes, as well as upon the adipose tissue, suggest that chronic stress, whether psychological and/or physical, exerts an intense effect upon body composition, which, in turn, significantly affects the longevity and survival of the organism.
 ...
PMID:Hypercortisolism and obesity. 859 40

The paper summarizes the studies documenting the outlasting of increased cardiovascular mortality in patients with Cushing's syndrome even after the hypercortisolism resolution. Despite the hypercortisolism resolution the mortality during the subsequent period of life is up to four-fold higher than in the comparable population as a whole. The pathogenesis of this cardiovascular risk is based on arterial hypertension, steroid cardiomyopathy and hyperlipidaemia with subsequent atherosclerosis. The post mortem material bears a parallel of the extent of atheromatous changes and duration of hypercorticolism. The prevention has to its disposition two mutually complementing means. The first is represented by clinical screening of hypercorticolism which enables an early recognition and therapy of the Cushing's syndrome. The successive measure resides in increased attention to the cardiovascular system even after hypercorticolism resolution. (Tab. 1, Fig. 1, Ref. 25.).
 ...
PMID:[Cushing's syndrome is still a potentially fatal disease]. 862 39

Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1C over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P < 0.0005), UFC and OGTT glucose area under the curve (AUC) (P < 0.01), and UFC and HbA1C (P < 0.005). UFC levels were negatively correlated (P < 0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the beta-cell.
 ...
PMID:Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM. 907 4

Lipodystrophies associated with HIV disease have been reported in recent years and have included a general redistribution of fat with more central fat and increased dorsocervical fat. These lipodystrophies are commonly associated with hyperlipidemia and in some cases with insulin resistant diabetes. Although a similar redistribution of fat is seen in hypercortisolism, in general, serum and urinary cortisol levels are normal in these HIV-positive patients. However cortisol/dehydroepaindrosterone (DHEA) ratios are increased in HIV disease and may result in a relative hypercortisolism. Seven HIV-positive male patients on multidrug antiviral therapy including HIV protease inhibitors had developed increased central and dorsocervical fat over 1 year. All patients had increased serum lipids and three had insulin resistant diabetes. Four patients were treated initially with DHEA 100-200 mg/day, with addition of a cyclo-oxygenase (COX) inhibitor (indomethacin 100 mg/day) and three others were treated from the onset with a combination of DHEA 200 mg/day and a COX inhibitor (indomethacin 100 mg/day or naprosyn 1000 mg/day). All patients reported moderation or normalization of their serum lipids and some moderation of blood sugars while on DHEA alone. More marked improvement in blood sugar and noticeable decreases in the dorsocervical fat; however, occurred only with addition a COX inhibitor. Both DHEA and COX inhibitors have a number of mechanisms of action; among these is their role as a peroxisome proliferator-activator receptor ligand. Dysregulation of peroxisome function is associated with the spectrum of biochemical changes seen within these HIV associated lipodystrophies. Use of HIV protease inhibitors is reported in the majority of patients with these lipodystrophies, and protease inhibitors may accentuate the underlying peroxisome dysregulation. Supplementation with DHEA and a COX inhibitor may improve peroxisomal function.
 ...
PMID:Peroxisomal proliferator-activated ligand therapy for HIV lipodystrophy. 1129 5

Corneal degeneration may occur with a deposition of lipids or calcium, or both. Calcareous and lipid degeneration may be either primary or secondary, associated with systemic diseases such as primary hyperlipidemia, hyperlipidemia associated with hyperadrenocorticism, and hypothyroidism. The authors report a case of bilateral corneal lipid and calcium degeneration in a 7-year-old female Poodle with hyperadrenocorticism. The condition worsened with Lysodren therapy but responded to surgical excision.
 ...
PMID:Combined corneal lipid and calcium degeneration in a dog with hyperadrenocorticism: a case report. 1194 Feb 51


1 2 Next >>