Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article discusses the factors that contribute most to systolic and diastolic heart failure (HF): ischemic heart disease, hypertension,obesity, diabetes, and nephropathy. Diabetes often follows the insulin resistance syndrome in which obesity and hypertension are combined with dyslipidemia, and obesity is likely causal. Diabetes and hypertension are common causes of nephropathy, which in turn is a common precursor to HF. Insulin resistance, obesity,dyslipidemia, diabetes, and hypertension are risk factors for atherosclerotic coronary disease and left ventricular ischemia. Each is also a risk factor for diastolic dysfunction.
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PMID:Lifestyle and dietary modification for prevention of heart failure. 1533 18

Ischemia / reperfusion (I / R) injury is related to tissue graft energy status. Insulin, which is currently used in the University of Wisconsin (UW) preservation solution with insulin (UWI), is an anabolic hormone and was shown to exacerbate the hepatic I / R injury in our previous study. In this study, the energy status and regulation of metabolism genes by insulin were investigated in liver grafts preserved by UW solution. Insulin could significantly decrease adenosine triphosphate (ATP) level after 3 hours of preservation, as well as total adenine nucleotides (TANs) and energy charge (EC) levels. Energy regeneration deteriorated in the grafts preserved by insulin in terms of ATP and EC levels at 24 hours after transplantation. The insulin signal was transduced through the insulin receptor substrate-2 (IRS-2) pathway and the activity of IRS-2 was decreased gradually at the messenger ribonucleic acid (mRNA) level during cold preservation. Downstream targeting genes such as sterol regulatory element-binding protein-1c (SREBP-1c), glucokinase (GKC), and fatty acid synthase (FAS) genes, as well as phospho-glycogen synthase kinase-3beta (GSK-3beta) were activated and they showed the similar expression profiles during cold preservation. Lipoprotein metabolism was accelerated by insulin through upregulation of the activity of apolipoprotein C-III (Apo C-III) during cold preservation. The insulin-like growth factor-binding protein-1 pathway was inhibited during cold preservation. In conclusion, insulin in UW solution exacerbates hepatic I / R injury by energy depletion as the graft maintains its anabolic activity. The key enzyme activities of the energy-consuming process of glycogen and fatty acid synthesis as well as lipoprotein metabolism were accelerated by insulin through the IRS-2 / SREBP-1c pathway.
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PMID:Insulin in UW solution exacerbates hepatic ischemia / reperfusion injury by energy depletion through the IRS-2 / SREBP-1c pathway. 1535 11

The heart is an insulin-responsive organ, and disorders of insulin action, such as diabetes and obesity, can have profound effects on cardiac performance. Insulin signaling influences numerous functions within the heart, such as metabolic substrate preference, cell size, and the response of the heart to ischemia and hypertrophy. Because the systemic consequences of altered insulin action can have significant but indirect effects on the heart, the generation of mice with altered expression of insulin receptors and key components of the insulin-signal transduction pathways in cardiomyocytes have led to interesting and occasionally surprising new insights into the regulation of cardiac biology by insulin.
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PMID:Insulin signaling in heart muscle: lessons from genetically engineered mouse models. 1552 84

The purpose of this study was to test whether the insulin sensitivity, lipid metabolism and the susceptibility of the heart to ischemia/reperfusion injury are modulated by the chronic estrogen status. Rats were ovariectomized (OVX), not ovariectomized (sham) or ovariectomized and treated with subcutaneous 17 -estradiol (30 mug/kg/day, OVX+E2) (n=14-17 per group). Within 3 months after operation, body weight, the serum levels of estrogen, glucose, insulin, total cholesterol (T-chol), HDL-chol, LDL-cholesterol (LDL-chol), triglycerides (TG) and lipoprotein a (Lp(a)) were monitored. Three months after operation, hearts of partial rats (n=6-8 per group) were isolated and allowed an initial 20-min stabilization period, and then cardiac function was recorded and creatine kinase (CK) release in the coronary effluent was measured after 4 h of hypothermic ischemia in isolated rat hearts. The experimental results showed that from 2 weeks after ovariectomy to the end of the study, body weights of OVX were significantly higher compared with the other two groups (p<0.05). On weeks 5 and 9, insulin level of OVX was significantly higher than that of the other two groups (p<0.05), whereas it was not different among the three groups on weeks 12 and 13 (p>0.05). Blood glucose on week 13 was significantly higher in OVX (p<0.05). Consequently, Insulin Sensitivity Index (ISI) of OVX was lower than that of the other two groups on weeks 5 and 9 (p<0.05), but not on weeks 12 and 13. Serum values for T-chol, HDL-chol and LDL-chol were not significantly different among the three groups within the observing period. On week 13, TG level in ovariectomized group was significantly lower than in the sham- and E2-treated groups (p<0.05). Compared with sham, Lp(a) level was slight increased in OVX rats (p<0.05), while it was further increased in E2-treated rats (p<0.05). Cardiac function (left ventricular pressure (LVP) and +/-dp/dtmax) of hearts removed from OVX rats was depressed, and CK release was markedly increased (p<0.05). However, treatment with E2 significantly improved cardiac function, as shown by increasing left ventricular pressure,+dp/dtmax and -dp/dtmax, and decreased CK release. In conclusion, chronic E2 treatment has some beneficial effects on cardiovascular disease (CVD), which come from the results of improvement of insulin sensitivity and post-ischemia cardiac function. However, the mechanism did not include changes in lipids and lipoproteins. The change in Lp(a) level shows that estrogen does not confer cardiovascular protection and may increase the risk of stroke.
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PMID:Influence of ovariectomy and 17beta-estradiol treatment on insulin sensitivity, lipid metabolism and post-ischemic cardiac function. 1556 37

Insulin-like growth factor-1 (IGF-I), the primary mediator of growth hormone (GH) effects, is an important regulator of cell growth, differentiation, and apoptosis. GH and IGF-I deficiency is known to be associated with premature atherosclerosis and elevated cardiovascular disease mortality. Recent evidence suggests that cardiovascular disease risk may also be elevated among apparently healthy individuals who have serum IGF-I levels in the low-normal range. In this review, we appraise the epidemiologic and clinical studies implicating low IGF-I level as a risk factor for incident myocardial infarction and other manifestations of coronary heart disease. Potential mechanisms that may underlie this association include beneficial effects of IGF-I on myocyte survival after ischemia, stability of atherosclerotic lesions, and endothelial function. We conclude that additional confirmatory data from prospective studies are needed to confirm low IGF-I level as an independent cardiovascular risk factor. However, if this finding is confirmed, this would support the rationale for intervention trials aimed at reducing cardiovascular disease morbidity and mortality among older adults by targeting the GH/IGF-I pathway.
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PMID:Insulin-like growth factors and coronary heart disease. 1559 27

The mechanisms responsible for cerebral edema formation in diabetic ketoacidosis (DKA) are not well understood, although evidence suggests ischemia as a contributing factor. Previous studies have shown that the Na-K-Cl cotransporter of cerebral microvascular endothelial cells and astrocytes is a major participant in ischemia-induced cerebral edema in stroke. The present study was conducted to test the hypothesis that the Na-K-Cl cotransporter also contributes to cerebral edema in DKA. Sprague-Dawley rats were administered streptozotocin to induce DKA, and then cerebral edema was assessed by determination of apparent diffusion coefficients (ADC) with magnetic resonance diffusion-weighted imaging. Cerebral ADC values in DKA rats were significantly reduced in both cortex and striatum compared with non-DKA control rats, indicating the presence of cerebral edema. Intravenous administration of bumetanide to DKA rats abolished the drop in cortical ADC values, while having no significant effect in the striatum. Insulin and saline treatment had no effect when given after bumetanide but increased both cortical and striatal ADC values when given before bumetanide. Evidence is also presented here that acetoacetate and beta-hydroxybutyrate stimulate brain microvascular Na-K-Cl cotransporter activity. These findings suggest that the Na-K-Cl cotransporter contributes to brain edema in DKA.
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PMID:Bumetanide reduces cerebral edema formation in rats with diabetic ketoacidosis. 1567 9

The elective global ischemia of on-pump coronary artery bypass surgery contributes to the incidence of postoperative mortality, complications, and use of resources. In addition to cardiopulmonary bypass and techniques for myocardial protection such as aortic cross clamp, ventricular fibrillation, and cardioplegia, the administration of systemic glucose-insulin-potassium (GIK) in the perioperative period may act as both a metabolic modulator and potential inodilator. GIK may therefore serve to protect the myocardium and promote adequate cardiac and hemodynamic performance that would improve patient recovery. Cell, tissue, and animal experiments have determined a number of mechanisms of action by which this may be achieved, with increasing focus on insulin as the key component. The original concepts centered on GIK during or after ischemia switching metabolism away from that based on non-esterified fatty acids toward a more favorable glucose-based metabolism and thus improving the efficiency of adenosine triphosphate production and glycogen preservation. Insulin's ability to reduce intracellular fatty acid metabolism may also reduce cellular membrane damage. More recently other mechanisms have also been suggested, including osmotic, oxygen free radical scavenging, and antiapoptotic and anti-inflammatory effects. However, trials that have examined the role of GIK in cardiac surgery have been small, open label, and involved a wide variety of regimens. They have demonstrated improved glycogen preservation, reduced infarct size, reduced incidences of dysrhythmias, need for inotropic agents, and low cardiac output state, and overall reduced lengths of stay. The perceived need to achieve strict blood glucose control to reduce neurologic injury and improve overall mortality have conflicted with its practical difficulties, particularly during cold cardiopulmonary bypass, and the exact role of supplemental glucose administration and resulting hyperglycemia require re-examination.
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PMID:Glucose and insulin influences on heart and brain in cardiac surgery. 1592 Jun 45

The purpose of the study was to investigate the character of clinical and functional manifestations of ischemic cardiac dysfunction in patients with idiopathic coronary microangiopathy, and their correlation with insulin level, as a possible diagnostic criterion of coronary heart disease (CHD). The subjects were 115 men, including 35 individuals (mean age 41.8 +/- 1.2 years) with microvascular form (MVF) of coronary artery lesion, 60 patients with CHD with postinfarction cardiosclerosis (PICS), and 20 healthy individuals. Patients with glucose tolerance disorder, diabetes mellitus, arterial hypertension, and other severe pathology were not included in the study. The diagnostic tests included selective coronaroventriculography with right ventricle endomyocardium biopsy, and myocardial perfusion scintigraphy. Parameters of coronary, intracardial and system hemodynamics were evaluated; insulin and glucose serum levels were measured at rest and during stress-tests with physical exercise. Endocardial biopsy in MVF patients found plastic insufficiency of the endothelium of hemocapillars, prearteriols and cardiomyocytes. Alterations in the parameters of metabolism, intracardial and system hemodynamics, and physical exercise tolerance were found to be comparable in MVF and PICS patients. Insulin level at rest in both groups was equal to that in the control group. At threshold physical load during veloergometry insulin levels in MVF and PICS patients demonstrated comparable elevation (222.8% and 201%, respectively; p < 0.05-0.01). Glucose concentrations in patients with microangiopathy decreased by 28% (p < 0.05), while in patients with CHD it increased significantly by 27.3% (p < 0.05). The study shows that structural and functional lesion of hemocapillar endothelium underlies cardiac syndrome X It results in perfusion ability impairment, chronic hypoxia, impairment of myocardial contractility under the conditions of physical activity. Hyperinsulinemia, manifesting when ischemia is induced, is not caused by insulinresistence. Probably, it presents and adaptive and compensatory reaction to increase of myocardial glucose requirement, and may be one of early CHD markers.
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PMID:[Hyperinsulinemia in patients with microvascular coronary artery lesion as a possible diagnostic criterion of coronary heart disease]. 1607 44

In myocardial damage due to ischemia-reperfusion, the administration of insulin together with glucose and potassium may be protective, although in some patients and animal models, it is ineffective. In a rat model (HTG) with characteristics of the metabolic syndrome, induced by sucrose feeding, ischemia-reperfusion of the isolated heart evidences a less favorable outcome than in control animals, particularly males. We investigated the effect of insulin infusion during the reperfusion period in isolated hearts from control and HTG male and female rats. Weanling Wistar rats were given commercial rat chow and tap water (C rats) or 30% sucrose solution (HTG rats) for 8 months. They developed moderate hypertension and hyperinsulinemia, central adiposity, nephropathy, and hypertriglyceridemia. Cardiac function was recorded in a Langendorff preparation subjected to 25 min ischemia and 15 min reperfusion. The handicapped functionality of HTG hearts is more apparent under conditions of stress. Insulin administration improved particularly mechanical work and +dp/dt max variables. The effect of sex was observed on the type of arrhythmias developed during reperfusion: Only the males showed lethal ventricular fibrillation, which disappeared after insulin administration. Females had lower levels of cardiac enzymes creatine kinase (CKMB) and lactic dehydrogenase (LDH), but their performance was not hindered, probably on account of protective factors such as estrogens. Summing up, the pathological features of the HTG model did not prevent insulin from exerting some of its beneficial effects in HTG hearts. Sex differences in the outcome were more apparent in the type of arrhythmias after reperfusion; they were lethal in HTG males only, but insulin prevented their onset.
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PMID:Isolated heart function during ischemia and reperfusion in sucrose-fed rats: effect of insulin infusion. 1616 99

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.
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PMID:Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease. 1644 88


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