Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction is a major characteristic of the atherosclerotic process and can be used to predict the outcome of cardiovascular disease in humans. Together with obesity and insulin resistance, such dysfunction is common among patients with type 2 diabetes and may explain their poor prognosis in connection with such a disease. Insulin resistance in skeletal muscle, adipose tissue, and the liver, a well-characterized feature of obesity and type 2 diabetes, contributes to the impairment of glucose homeostasis. Furthermore, the myocardial muscle can also be resistant to insulin, which might, at least in part, explain the frequent development of heart failure in individuals suffering from type 2 diabetes. The relationship between insulin resistance and endothelial dysfunction has prompted investigations, which reveal that regular exercise, dietary changes, and/or pharmacological agents can both increase insulin sensitivity and improve endothelial function. Glucagon-like peptide-1, an incretin, lowers blood levels of glucose and offers a promising new approach to the treatment of type 2 diabetes mellitus. Its extensive extra-pancreatic effects, including a favorable influence on cardiovascular parameters, are extremely interesting in this connection. The potential pharmacological effects of glucagon-like peptide-1 and its analogues on the endothelium and the heart are discussed in the present review.
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PMID:The potential beneficial role of glucagon-like peptide-1 in endothelial dysfunction and heart failure associated with insulin resistance. 1879 70

The Insulin-like growth factor-1 (IGF-1) system is dynamic and complex, involving many binding proteins, binding-protein-related proteases, and receptors. It has emerged in time as a powerful defence to life processes of many cytotypes, tissues and systems. Mainly in body metabolism, diabetes and cardiovascular system, but also in brain and kidney, IGF-1 plays a key role in maintaining homeostasis, increasing progenitor cell potential, and improving physiologic performance both in rest and stress conditions. Its vasculoprotective and insulin sensitizing ability exerts a protective role on flow-metabolism coupling and organs function. Therapeutical human use of recombinant human IGF-1 (rhIGF-1) has been widely applied only in Laron syndrome, while being verified in many randomized controlled trials to improve glycemic control in type 1 and type 2 diabetes, and proposed in neurological disease such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer disease. Sparse evidence exists moreover about rhIGF-1 use in insulin resistance, burns, catabolic and post-surgery states, acute and chronic renal failure, amyotrophic lateral and multiple sclerosis, brain injury, and immunoincompetence. Along with these data, results are available on cardiovascular benefit of administration of other growth factors, such as erythropoietin and vascular endothelial growth factor, or on cardiovascular side effects of growth factor antagonists such as trastuzumab in cancer therapy. We intended therefore to summarize in this review available human and animals evidence about rhIGF-1 effects on different systems with insights on rhIGF-1 cardiovascular effects. In view of its ability to improve flow-metabolism coupling, IGF-1 could indeed represent a new cardiovascular disease treatment option for many cardiac disorders such as ischemic heart disease and heart failure.
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PMID:Recombinant human insulin-like growth factor-1: a new cardiovascular disease treatment option? 1885 38

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.
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PMID:A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload. 1897 96

The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-zeta/lambda and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.
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PMID:Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature death. 1900 Oct 90

Insulin resistance is prevalent in heart failure (HF) patients, and beta2 adrenergic receptors (beta2-AR) are involved in glucose homeostasis. We hypothesized that beta2-AR Gln27Glu and Arg16Gly polymorphisms affect insulin resistance in HF patients, and we explored if effects of beta2-AR polymorphisms on glucose handling are modified by choice of beta blocker. We studied 30 nondiabetic adults with HF and a history of systolic dysfunction; 15 were receiving metoprolol succinate, and 15 were receiving carvedilol. We measured fasting glucose, insulin, and insulin resistance, and we determined beta2-AR genotypes at codons 27 and 16. The cohort was insulin resistant with a mean HOMA-IR score of 3.4 (95% CI, 2.3 to 4.5; normal value, 1.0). Patients with the Glu27Glu genotype exhibited higher insulin and HOMA-IR compared to individuals carrying a Gln allele (P = 0.019). Patients taking carvedilol demonstrated lower insulin resistance if also carrying a wild-type allele at codon 27 (fasting insulin, 9.8 +/- 10.5 versus 20.5 +/- 2.1 for variant, P = 0.072; HOMA-IR, 2.4 +/- 2.7 versus 5.1 +/- 0.6, P = 0.074); those on metoprolol succinate had high insulin resistance irrespective of genotype. The beta2-AR Glu27Glu genotype may be associated with higher insulin concentrations and insulin resistance in patients with HF. Future studies are needed to confirm whether treatment with carvedilol may be associated with decreased insulin and insulin resistance in beta2-AR codon 27 Gln carriers.
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PMID:The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker. 1903 36

Progressive ventricular hypertrophy can lead to the development of insulin resistance, a feature of both chronic kidney disease and heart failure. Here we induced uremia in adult male Sprague-Dawley rats using a remnant kidney model and studied the expression of glucose transporters. As expected, the reduction of nephron mass resulted in impaired renal function, cardiac hypertrophy, glucose intolerance, hyperinsulinemia, anemia, and hypertension. Insulin sensitivity was significantly reduced in the uremic animals as determined by oral glucose tolerance tests. After six weeks of uremia, at a point when cardiac hypertrophy had been established, left ventricle tissue had a marked increase in the expression of GLUT4 (insulin-dependent glucose transporter 4), consistent with hypertrophic remodeling, but not GLUT1 (insulin-independent glucose transporter 1). However, although uremic animals had systemic insulin resistance and glucose intolerance, there was no evidence of impaired GLUT4 translocation in the heart at 6 weeks of uremia, suggesting that other mechanisms may underpin insulin resistance in the uremic heart.
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PMID:Insulin resistance and altered glucose transporter 4 expression in experimental uremia. 1917 56

The aim was to evaluate management and outcomes in patients with diabetes mellitus (DM) with acute coronary syndrome (ACS). The EHS-ACS-II was a multinational survey conducted in 2004 that included 6,385 consecutive patients with ACS. The management and outcomes of patients with and without DM were compared. DM was recognized in 1,587 patients (25%) with ACS. Patients with DM had a less favorable risk-factor profile, less typical presentation, and longer delay in seeking medical attention; presented more frequently with arrhythmias, heart failure, renal failure, and major bleeding; and had higher in-hospital and 1-year mortality. They were treated more often with diuretics and inotropic agents and less often with antiaggregants (glycoprotein IIb/IIIa and clopidogrel). Insulin was administered to 53% of patients with DM during hospitalization and 31% at discharge. Patients with DM with ST-elevation (STE) myocardial infarction underwent similar primary percutaneous and coronary interventions (but received less thrombolytic therapy). Patients with DM with non-STE ACS underwent less in-hospital revascularization and had significantly higher 1-year mortality. Multivariable analyses showed DM as a predictor of 1-year mortality (odds ratio 1.37, 95% confidence interval 1.09 to 1.71), but not in-hospital mortality. In conclusion, given the current treatment, patients with and without DM with ACS had similar in-hospital adjusted mortality, but patients with DM had increased 1-year mortality. Patients with DM with non-STE ACS posed a higher risk group.
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PMID:Comparison of treatment and outcome of acute coronary syndrome in patients with versus patients without diabetes mellitus. 1926 30

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) might play a pathogenic role in heart failure. We showed significantly increased myocardial IGFBP-3 expression (investigated by real-time polymerase chain reaction) and apoptosis (detected by flow cytometry) in 23 failing hearts from patients undergoing cardiac transplantation for end-stage dilated or ischemic cardiomyopathy, when compared with 10 controls. Higher IGF-1 mRNA levels were shown only in end-stage dilated cardiomyopathy.
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PMID:Myocardial insulin-like growth factor-1 and insulin-like growth factor binding protein-3 gene expression in failing hearts harvested from patients undergoing cardiac transplantation. 1933 70

Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. It plays a role in various diseases, including autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases and type 1 diabetes, as well as in diseases associated with metabolic syndrome such as atherosclerosis, chronic heart failure and type 2 diabetes. Macrophage are the primary source of IL-1, but epidermal, epithelial, lymphoid and vascular tissues also synthesize IL-1. IL-1beta production and secretion have also been reported from pancreatic islets. Insulin-producing beta-cells within pancreatic islets are specifically prone to IL-beta-induced destruction and loss of function. Macrophage-derived IL-1beta production in insulin-sensitive organs, leads to progression of inflammation and induction of insulin resistance in obesity. We summarize the mechanisms involved in inflammation and specifically the IL-1beta signals that lead to the progression of insulin resistance and diabetes. We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes.
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PMID:Interleukin-1 beta targeted therapy for type 2 diabetes. 1960 25

BACKGROUND: Abnormal glucose metabolism and insulin resistance have been associated with heart failure incidence, severity, and mortality. Metabolic parameters such as hepatic glucose production may be altered by beta-adrenoceptor antagonists in patients with heart failure. OBJECTIVE: This study evaluated the effects of metoprolol or carvedilol up-titration on fasting glucose, insulin resistance and beta(2)-mediated glucose production in patients with chronic heart failure. METHODS: This was a prospective, randomized, active comparator study in 15 patients with AHA/ACC Stage C systolic dysfunction HF stable on medical therapy. Participants were randomized to metoprolol 25mg daily or carvedilol 3.125mg twice daily. Metoprolol was titrated to a target of 200mg daily, and carvedilol was titrated to 25mg twice daily over 8weeks. Insulin resistance as assessed by the homeostatic model, and terbutaline-induced glucose production (AUC(0-180)), were assessed at baseline and at 4 subsequent beta-blocker titration visits over 8 weeks. RESULTS: In all 15 patients, terbutaline-induced glucose AUC(0-180) decreased (p=0.0006) as beta-blocker doses increased. A significant reduction in glucose AUC(0-180) compared to baseline was only noted in patients taking metoprolol at 100mg daily (-2424.6 [95% CI -372.6 to -4478.4] mg/dL*min) and 200mg daily (-2437.2 [95% CI -15.1 to -4604.4] mg/dL*min), and not observed in those taking carvedilol. After beta-blocker titration, fasting glucose concentrations for the metoprolol and carvedilol groups were 86.9 (95% CI 89.8-101.6) mg/dL and 95.7 (95% CI 89.8-101.6) mg/dL, respectively (p=0.0273), adjusted for baseline values. There was no significant difference between metoprolol and carvedilol on insulin resistance. CONCLUSION: Increasing doses of beta-blockers are associated with decreased in beta2-mediated glucose production in heart failure. Metoprolol, but not carvedilol, decreases hepatic glucose production at commonly used heart failure doses.
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PMID:Effects of Beta-Blocker Titration on Glucose Homeostasis in Heart Failure. 1967 80


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