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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The concentrations of the serum lipoproteins were significantly increased, while, only small changes in the distribution of the serum lipids and the composition of the lipoproteins were observed. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP was higher in cells derived from the rats with the tumor, although the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP no difference was observed between the control and tumor bearing groups. Clofibrate administered in the diet resulted in a complete elimination of the tumor effect on serum triglycerides and to a great extent prevented the rise in serum cholesterol. The tumor-induced increase in the concentration of the high density lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was partially reversed. The increased lipolytic response and accumulation of cyclic AMP following stimulation by ACTH was not altered in adipocytes derived from tumor bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin or serum lipids in the control rats nor were the elevated hormone levels of the tumor bearing rats changed.
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PMID:Experimental hyperlipidemia in rats. 22 51

The investigations were carried out in 30 patients with primary hyperlipidaemia (hypercholesterolaemia, hypertriglyceridaemia and mixed form). The serum total cholesterol and triglycerides, and in the erythrocytes the levels of AMP, ADP, ATP, ATP complex with Fe, MP, HDP and DGP were determined. Twenty blood donors served as a control group. The obtained results showed a statistically highly significant rise in ADP concentration in all investigated subgroups of hyperlipidaemic subjects, and a non-significant quantitative shift of other determined phosphate compounds.
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PMID:Certain phosphate compounds in the erythrocytes of patients with primary hyperlipidaemia. 50 54

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension.
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PMID:Cyclic nucleotides and platelet aggregation in hypertensive rats with ectopic pituitary tumor. 624 46

It was shown that 7 to 10 days' injection of lipoproteins (LPs), isolated from the human blood serum according to Burstein and Scholnick method, induces significant inhibition of the rat thyroid iodine-absorbing function. Alpha-LPs exert more evident inhibiting effect than beta + pre- beta-LPs, and beta + pre- beta-LPs from the oncological patients' blood serum have more pronounced inhibiting effect comparatively to the same fraction of the donors; blood serum. 10-days' LP injection is accompanied by thyroxine inhibition and iodothyrozine/iodothyronine ratio rise in the thyroid tissue. In the experiments in vitro and in vivo several Lp fractions decreased thyrotropin-stimulating effect on AMP accumulation in the rat thyroid gland. Possible mechanisms of LP action on the thyroid function are discussed. The study of LP effect on the thyroid function in homologous system is necessary. It is suggested that hyperlipidemia (hyperlipoproteinemia) is one of the factors, contributing to the thyroid function decrease with age and in patients with malignant tumors.
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PMID:[Effect of human serum lipoproteins on various indices of thyroid function in rats]. 628 36

Cardiovascular complications of obesity are more common in men than women. Sex differences in visceral fat lipolysis may be of importance in this respect, since increased release of free fatty acids (FFAs) from visceral fat to the liver by the portal venous system has been thought to cause several metabolic complications due to obesity, such as hypertension, hyperlipidemia, and glucose intolerance. The aim of this study was to investigate sex differences in clinical characteristics and visceral fat mobilization in obesity. Obese subjects (22 male and 23 female) undergoing elective surgery were matched for body mass index and age. The males had both higher waist-to-hip ratio (WHR), sagittal diameter, blood pressure, fat-cell volume, plasma insulin, glucose, and triglyceride and lower HDL cholesterol levels than the females. The rate of norepinephrine-induced FFA and glycerol release was twofold higher in men (P = .02). No significant reutilization of FFA was observed. The difference in maximum norepinephrine-induced rate of lipolysis between men and women was independent of both WHR and sagittal diameter and was an independent regressor for levels of plasma glucose and plasma HDL cholesterol. Fat-cell volume was an independent regressor for plasma triglycerides and blood pressure. No sex differences in the lipolytic sensitivity to beta 1- or beta 2-adrenoceptor-specific agonists or in the antilipolytic effect of insulin were observed. However, the lipolytic beta 3-adrenoceptor sensitivity was 12 times higher (P = .004) and the antilipolytic alpha 2-adrenoceptor sensitivity 17 times lower (P = .003) in men. Furthermore, lipolysis induced by agents acting at the adenylate cyclase and protein kinase A levels were almost twofold enhanced in men. However, no sex difference in maximum hormone-sensitive lipase activity was observed. In conclusion, in obesity, catecholamine-induced rate of FFA mobilization from visceral fat to the portal venous system is higher in men than women. This phenomenon is partly due to a larger fat-cell volume but also to a decrease in the function of alpha 2-adrenoceptors, an increase in the function of beta 3-adrenoceptors, and an increased ability of cyclic AMP to activate hormone-sensitive lipase. These factors may contribute to gender-specific differences in metabolic and cardiovascular disturbances accompanied by obesity.
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PMID:Sex differences in visceral fat lipolysis and metabolic complications of obesity. 926 Dec 82

One of the characteristics of obesity-associated diabetes is an elevated fasting plasma insulin concentration with a weak insulin secretory response to subsequent glucose stimulation. Evidence suggests that hyperglycemia and hyperlipidemia may contribute to the initiation and progression of this disordered islet glucose sensing. It has been proposed that reducing hyperglycemia and hyperlipidemia per se may improve islet glucose sensing. Here we studied glucose-dependent insulin release in islets isolated from ob/ob mice treated with dopamine agonists (bromocriptine and SKF38393, BC/SKF) which significantly reduced circulating glucose and lipid levels of ob/ob mice. Islets from BC/SKF-treated mice showed a marked decrease of the elevated basal insulin release to levels similar to lean mice. Such treatment also induced a higher secretory response to glucose stimulation compared with that in ob/ob mice with sustained hyperglycemia and hyperlipidemia. Similarly, when islets from untreated ob/ob mice were cultured for 7 days in 11 mM glucose in the absence of free fatty acid, the basal insulin release was significantly decreased and high glucose stimulated insulin release increased compared with that from islets cultured in medium containing 30 mM glucose and 2 mM oleate. The BC/SKF-induced reduction of elevated basal insulin release was associated with decreased hexokinase activity and basal cyclic AMP content in islet tissue. Our results demonstrate that dopamine agonist treatment improves basal insulin release in ob/ob mice and this effect may be mediated, in part, by a reduction of hyperglycemia and hyperlipidemia.
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PMID:Dopamine agonist treatment ameliorates hyperglycemia, hyperlipidemia, and the elevated basal insulin release from islets of ob/ob mice. 978 90

Herein are described the development and certain properties of a new drug, pyrazinoylguanidine (PZG), intended for use as an adjunct in the treatment of hypertensive patients with type 2 diabetes, formerly called noninsulin dependent diabetes mellitus. PZG is an analog of the potassium sparing diuretic, amiloride. However, in diabetic patients, amiloride exacerbates hyperglycemia and hyperlipidemia, whereas PZG reduces them. In several studies, PZG not only reduced elevated blood pressure in subjects with essential hypertension, but also downregulated the glucose fatty acid cycle in hypertensive patients with type 2 diabetes. PZG was well tolerated in all patients, as well as in normal subjects whose blood pressures and glucose metabolism were unaffected by PZG. However, in normal subjects made hyperglycemic by giving them hydrochlorothiazide, coadministration of PZG returned blood glucose concentrations to normal. Mechanisms for these effects of PZG in human subjects were investigated in both normal Sprague-Dawley rats and rats made diabetic with streptozotocin (STZ). In isolated rat adipocytes stimulated with theophylline, PZG downregulated both lipolysis and cyclic AMP concentrations. PZG, as well as insulin, increased adipose cyclic nucleotide phosphodiesterase activity, whereas theophylline reduced it. In perfused rat liver, PZG decreased gluconeogenesis and cyclic AMP concentrations. Collectively, these studies illustrate how the side effects (toxicity) of certain drugs, such as the tendency of thiazide diuretics to cause hyperglycemia and hyperlipidemia, can be modulated and even reversed by slight changes in the chemical structure of the molecule, specifically by removal of the 3,5-diamino and 6-chloro substituents on the benzene ring of amiloride to produce PZG.
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PMID:Studies on pyrazinoylguanidine: a novel antihypertensive, hypoglycemic and lipolytic drug intended for adjunctive use in hypertensive patients with type 2 diabetes mellitus. 1078 66

Obesity, a state of increased adipose tissue mass, is a major cause for type 2 diabetes, hyperlipidemia, and hypertension, resulting in clustering of risk factors for atherosclerosis. Heterozygous PPARgamma knockout mice and KKA(y) mice administered with a PPARgamma antagonist were protected from high-fat diet-induced adipocyte hypertrophy and insulin resistance. Moderate reduction of PPARgamma activity prevented adipocyte hypertrophy, thereby diminution of TNFalpha, resistin, and FFA and upregulation of adiponectin and leptin. These alterations led to reduction of tissue TG content in muscle/liver, thereby ameliorating insulin resistance. Insulin resistance in the lipoatrophic mice and KKA(y) mice were ameliorated by replenishment of adiponectin. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes, but not the obesity of ob/ob mice. Furthermore, targeted disruption of the adiponectin gene caused moderate insulin resistance and glucose intolerance. In muscle, adiponectin activated AMP kinase and PPARgamma pathways, thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated muscle insulin resistance. In the liver, adiponectin also activated AMPK, thereby downregulating PEPCK and G6Pase, leading to decreased glucose output from the liver. In conclusion, PPARgamma plays a central role in the regulation of adipocyte hypertrophy and insulin sensitivity. The upregulation of the adiponectin pathway by PPARgamma may play a role in the increased insulin sensitivity of heterozygous PPARgamma knockout mice, and activation of adiponectin pathway may provide novel therapeutic strategies for obesity-linked disorders such as type 2 diabetes and metabolic syndrome.
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PMID:[The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism]. 1450 Nov 64

Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. This review will address the biology, actions, and regulation of three adipocyte hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an emphasis on the most recent literature. The main biological role of leptin appears to be adaptation to reduced energy availability rather than prevention of obesity. In addition to the well-known consequences of absolute leptin deficiency, subjects with heterozygous leptin gene mutations have low circulating leptin levels and increased body adiposity. Leptin treatment dramatically improves metabolic abnormalities (insulin resistance and hyperlipidemia) in patients with relative leptin deficiency due to lipoatrophy. Leptin production is primarily regulated by insulin-induced changes of adipocyte metabolism. Dietary fat and fructose, which do not increase insulin secretion, lead to reduced leptin production, suggesting a mechanism for high-fat/high-sugar diets to increase energy intake and weight gain. ASP increases the efficiency of triacylglycerol synthesis in adipocytes leading to enhanced postprandial lipid clearance. In mice, ASP deficiency results in reduced body fat, obesity resistance, and improved insulin sensitivity. Adiponectin production is stimulated by thiazolidinedione agonists of peroxisome proliferator-activated receptor-gamma and may contribute to increased insulin sensitivity. Adiponectin and leptin cotreatment normalizes insulin action in lipoatrophic insulin-resistant animals. These effects may be mediated by AMP kinase-induced fat oxidation, leading to reduced intramyocellular and liver triglyceride content. The production of all three hormones is influenced by nutritional status. These hormones, the pathways controlling their production, and their receptors are promising targets for managing obesity, hyperlipidemia, and insulin resistance.
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PMID:Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. 1474 80


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