Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as one of the most common causes of chronic liver damage in the western world. It is strongly associated with insulin resistance, obesity and other features of the metabolic syndrome. The entity NAFLD embraces a clinical spectrum from benign steatosis over steatohepatitis to hepatic cirrhosis with its complications liver failure and hepatocellular carcinoma. Treatment is currently based on prescriptive diet and physical exercise. A well-defined pharmacotherapy of NAFLD still remains to be established due to the lack of randomized, controlled trials. Yet, for several drugs such as Metformin and Thiazolidinediones, smaller trials report promising results.
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PMID:[Therapeutic options for nonalcoholic fatty liver disease and steatohepatitis]. 1624 33

A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemo-preventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.
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PMID:Use of microarray biomarkers to identify longevity therapeutics. 1644 42

Metformin is a biguanide. Due to its effects in suppressing the hepatic production of endogenous glucose and in increasing insulin sensitivity in adipose tissue and skeletal muscle, the agent is used particularly in type 2 diabetes mellitus and metabolic syndrome, in which insulin resistance is especially pronounced. Lactic acidosis is one of the most important side effects of metformin. A male patient, born in 1923, was admitted to the emergency unit of our hospital for sudden vertigo, weakness, dyspnea, cyanosis, and lethargy. His history data showed that the patient had been suffering from type 2 diabetes mellitus for 10 years and taking Glargin (insulin), 12 U/kg, once daily and Glucophage (metformin), 850 mg thrice daily. The patient's general condition was fair; stupor, time and spatial orientation were absent. Analysis of arterial blood gases showed the presence of metabolic acidosis, hypokalemia, hypoxemia, and hypercapnia. Thereafter the patient was transferred to the intensive care unit of the hospital; intubated and connected to a T-bird ventilation apparatus. On the following day, an analysis of arterial blood gases indicated the proximity of the results to their physiological parameters. Ventilation was stopped; and monitoring of the patient continued by following the T-shape type of ventilation discontinuation. There were no X-ray signs of pneumonia or pulmonary edema. On the same day, the patient was extubated and oxygen inhalation in a dose of L/min was continued through a mask. On day 4 since therapy was initiated, the patient's vital signs, serum sugar and lactate levels became normal. By determining a new treatment regimen, the patient was discharged from the intensive care unit. Dyspnea, acidosis, and hypoxia developed in the patient resulted from lactic acidosis caused by the use of metformin. It should be remembered that dyspnea, acidosis, and hypoxia, which suddenly developed in metformin-treated patients with type 2 diabetes mellitus, may be caused by lactic acidosis.
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PMID:[A clinical case of development of lactic acid acidosis in a diabetic patient taking metformin]. 1675 49

Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.
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PMID:[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance]. 1676 25

Metabolic and non metabolic cardiovascular risk factors tend to cluster in the same individual. The association of the cardiovascular risk factors is referred as metabolic syndrome (MS). This syndrome is associated with an increased risk of accelerated atherosclerosis and cardiovascular events. The cluster of cardiovascular risk factors of the MS includes: insulin resistance with or without glucose intolerance or diabetes, abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, a proinflammatory and prothrombotic state. MS is one of the major issues in the management of cardiovascular disease because of its epidemic proportion and its impact on increasing risk of developing both cardiovascular disease and type 2 diabetes. The main therapeutic goal in the management of patients with the MS is to reduce risk for clinical cardiovascular events and to prevent type 2 diabetes. In particular, for individuals with established diabetes, risk factors management must be intensified to reduce their higher cardiovascular risk. Lifestyle changes have a critical role in the clinical management of the risk factors predisposing to MS, such as overweight/obesity, physical inactivity. A large body of evidence suggests the use of Metformin and Acarbose for the treatment of the syndrome as these drugs have consistently shown to reduce cardiovascular events and mortality. Most anti-hypertensive drugs have unfavorable metabolic profile while b-blockers, centrally acting agents and drugs targeting the renin angiotensin system should always be considered for the treatment of hypertension in patients with MS.
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PMID:Metabolic syndrome. 1685 17

The metabolic syndrome (MS), a cluster of risk factors, such as obesity, hyperglycemia, hypertension and dyslipidemia, contributes to the development of cardio-vascular diseases and type 2 diabetes mellitus (DM2). Insulin resistance (IR) plays a key role in MS being strongly linked to abdominal visceral fat. Treatment for obese patients with MS should aim at improving IR, delaying the onset of DM2 and at reducing cardio-vascular risk. Weight loss, first therapeutic target, may be obtained through life-style modifications and anti-obesity drugs or bariatric surgery, at need. In these patients drug therapy is necessary if therapeutic life-style changes are not sufficient. Some drugs have adverse metabolic effects, therefore the therapeutic choices must be specific and rational. Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only). Also Angiotensin II receptor blockers and Angiotensin-converting enzyme inhibitors reduce the incidence of DM2 and insulin resistance and they are first-line antihypertensive drugs in MS. Calcium channel blockers, Alpha-1 antagonists and Alpha-2 agonists drugs are metabolically neutral and slight weight gains are related to the hydro-sodium retention. Beta-blockers and Diuretics, except for Indapamide and Anti-aldosterone drugs, can reduce insulin sensitivity, impair lipid profile and increase DM2 incidence; they are not first-line therapy yet they are necessary in selected cases only. Statins, Fibrates and omega-3 Fatty acids are indicated to normalize dyslipidemia. Low doses of acetylsalicylic acid are also recommended.
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PMID:[Therapeutic options for metabolic syndrome in obese patients]. 1806 54

Cardiovascular diseases continue to be the main cause of death in most industrialized countries. Endothelial dysfunction, a systemic process, is the earliest known marker of atherosclerosis and has become a major focus in acute ischemic disorders. We are investigating the hypothesis that, in these diseases, microvascular and endothelial dysfunctions occur simultaneously and precede the onset of macrovascular disease. We studied, to our knowledge for the first time in the same subjects, microvascular and endothelial functions in 11 patients with type 2 diabetes. 36 metabolic syndrome patients (NCEP-ATPIII criteria) and 25 young obese women matched with healthy controls. Micro vascular morphology and hemodynamics were evaluated non-invasively by means of nailfold videocapillaroscopy. Red blood cell velocity (RBCV, mm/s) was measured at rest and after release from 60 s of arterial occlusion (RBCVmax, mm/s) at the finger base, along with the time to reach RBCVmax (TRBCVmax, s), by video analysis with Cap Image software. Venous occlusion plethysmography was performed after intra-arterial infusions of acetylcholine and sodium nitroprusside to assess endo thelial-dependent and -independent vasodilation, respectively. We found similar results in the three groups of subjects, namely a significant decrease in RBCVmax, an increase in TRBCVmax, and a decrease in endothelial-dependent vasodilation. These findings clearly demonstrate that the two dysfunctions occur simultaneously in these groups of patients. Several mechanisms which could impair micro vascular and endothelial functions are associated with insulin resistance, and drugs that act on insulin resistance might thus be beneficial. Metformin, given to 16 first-degree relatives of patients with type 2 diabetes mellitus, who had the metabolic syndrome and normal glucose tolerance (ADA criteria), improved endothelial-dependent vasodilation and microcirculatory function. Rosiglitazone, given to 18 patients with the metabolic syndrome, enhanced vascular responses by improving endothelial function and increasing adiponectin levels. Increased triglyceride storage is often associated with insulin resistance, contributing to free fatty acid (FFA) overexposure. The two drugs tested here stimulate AMP-activated protein kinase, which promotes FFA oxidation and thus reduces oxidative stress, and might therefore attenuate endothelial lipotoxicity. The results strongly suggest that targeting micro vascular and endothelial dysfunctions in patients with metabolic disorders might help to prevent cardiovascular events, and warrant long-term clinical trials.
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PMID:[Vascular dysfunction in metabolic disorders: evaluation of some therapeutic interventions]. 1807 49

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.
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PMID:AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. 1819 20

Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection between both therapies may be the AMP-activated protein kinase (AMPK). This enzyme was originally described as a sensor of cellular energy status, being activated in exercise. On the other hand, several experimental evidences indicate that AMPK may be an important target of metformin action. This paper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species. AMPK activation determines a wide variety of physiological effects, including enhanced glucose uptake by skeletal muscle and enhanced lipid catabolism. Thus, it may be a key player not only in the prevention and treatment of DM2, but also in the development of new treatments for obesity and the metabolic syndrome. The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.
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PMID:[Metformin and AMPK: an old drug and a new enzyme in the context of metabolic syndrome]. 1834 5

The Zucker fatty (ZF) rat is a disease model of obesity and metabolic syndrome, such as hyperlipidemia and insulin resistance, resulting from hyperphagia owing to the loss of function of the leptin receptor, but it rarely develops hyperglycemia. We examined the effects of different doses of streptozotocin (STZ). A low dosage of STZ (30 mg/kg body weight, i.p.) elevated blood glucose levels in ZF rats up to 300 mg/dl within a week, and to nearly 500 mg/dl by 5 weeks after injection of STZ. Besides hyperglycemia, STZ-treated ZF (STZ-ZF) rats retained metabolic syndrome features such as hyperlipidemia and hyperinsulinemia. The stimulated insulin secretion in response to orally-loaded glucose disappeared completely in STZ-ZF rats. Although there were no significant differences in the morphology of pancreatic islets between vehicle-treated ZF (Cont-ZF) and STZ-ZF rats, the insulin content was markedly decreased in STZ-ZF rats. The hepatic gene expression for gluconeogenic enzymes was upregulated in STZ-ZF rats compared with Cont-ZF rats. Metformin lowered the blood glucose levels of STZ-ZF rats in a dose-dependent manner. These results suggest that STZ-ZF rats are useful for studies of T2DM and for the evaluation of the efficacy of anti-diabetic drugs.
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PMID:Characterization of STZ-Induced Type 2 Diabetes in Zucker Fatty Rats. 1863 56


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