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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fasting and postglucose hyperinsulinemia are recognized risk factors for acute coronary events. The insulin reactivity of patients with acute coronary syndromes, however, has not been carefully compared with that of patients with chronic stable angina. We used Bergman's minimal model to analyze the insulin response to intravenous glucose in 21 subjects: 8 patients with previous (>3 months) acute coronary syndrome but no effort-related angina; 6 patients with stable effort angina but no prior acute event; and 7 healthy controls. Diabetes mellitus, systemic hypertension, dyslipidemias, and obesity were excluded. All patients underwent coronary angiography. Insulin sensitivity, glucose effectiveness, and glucose tolerance were determined from insulin and glucose concentrations measured frequently up to 3 hours after a 0.33 g/kg intravenous glucose bolus. Patients with previous unstable angina or acute myocardial infarction had less extensive disease at angiography than patients with stable angina (p = 0.007). Both patient groups had higher basal and 180-minute insulinemia than controls (p <0.0007). However, patients with stable angina did not differ significantly from controls with regard to early and late insulinemic response to glucose. In contrast, patients with previous acute onset of ischemia had significantly greater 180-minute integrated insulinemia (p = 0.04) and reduced insulin sensitivity (p = 0.05) after the glucose challenge than did the stable angina group. These data suggest that patients with acute presentation of coronary artery disease, compared with patients with uncomplicated chronic stable angina, have an impaired insulin response to glucose despite less extensive coronary disease at angiography.
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PMID:Comparison of insulin response to intravenous glucose in healed myocardial infarction, in "cooled-off" unstable and stable angina pectoris, and in healthy subjects. 1053 2

Endothelial cell progenitors, angioblasts, have been detected in the peripheral blood of adult humans, mice, and rabbits. These cells have been shown to incorporate into the endothelium of newly forming blood vessels in pathological and nonpathological conditions. Here we investigated the possibility that the CD34-expressing leukocytes (CD34(+) cells) that appear to be enriched for angioblasts could be used to accelerate the rate of blood-flow restoration in nondiabetic and diabetic mice undergoing neovascularization due to hindlimb ischemia. CD34(+) cells did not accelerate the restoration of flow in nondiabetic mice, but dramatically increased it in diabetic mice. Furthermore, CD34(+) cells derived from type 1 diabetics produced fewer differentiated endothelial cells in culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In vitro experiments suggest that hyperglycemia per se does not alter the ability of angioblasts to differentiate or of angioblast-derived endothelial cells to proliferate. In contrast, hyperinsulinemia may enhance angioblast differentiation but impair angioblast-derived endothelial cell survival or proliferation. Our findings suggest that CD34(+) cells may be a useful tool for therapeutic angiogenesis in diabetics.
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PMID:Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. 1095 32

Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 microgram/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 microgram, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in ! lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexare! lin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.
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PMID:Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats. 1097 47

Cellular swelling has emerged as an important initiator of metabolic and proliferative changes in various cells. Because of the unique regenerative capacity of the adult liver, researchers have delineated key intracellular signals that are activated following mitogens, injury, and partial hepatectomy. Although hepatocellular swelling is commonly observed following these regenerative stimuli, only recently has the relationship between cell volume increase and proliferative activity been investigated; to date, the data implicating cell volume increase with hepatocyte regeneration has been mostly indirect. Hepatocyte swelling has been demonstrated in various clinical scenarios from sepsis, hepatic resection, ischemia-reperfusion injury, glucocorticoid excess, and hyperinsulinemia. Using various in vivo and in vitro models of hepatocyte swelling, particularly hypo-osmotic stress, investigators have demonstrated changes in cellular structure: (1) cell membrane stretch, (2) cytoskeletal microtubule and microfilament reorganization, and (3) alterations in cytoskeletal-membrane complexes. Similar studies have demonstrated a causal relationship between cell volume increase and intracellular signals: (1) activation of cytoplasmic signaling cascades such as MAPKs, PI-3-K, and PKC, (2) activation of proliferative transcription factors NF-kappaB, AP-1, STATs, C/EBPs, and (3) transcription of metabolic and immediate early genes of regeneration. Through mechanotransduction, or the translation of physical changes to chemical signals, cell volume is a potent effector of these signaling events. Growing evidence demonstrates a link between these physical and chemical changes in the swelling-mediated growth in the liver.
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PMID:Impact of cell swelling on proliferative signal transduction in the liver. 1150 Sep 54

The high energy demands of myocardium are met through the metabolism of lipids and glucose. Importantly, enhanced glucose utilization rates are crucial adaptations of the cardiac cell to some pathological conditions, such as hypertrophy and ischemia, but the effects of undernutrition on heart glucose metabolism are unknown. Our previous studies have shown that undernutrition increases insulin-induced glucose uptake by skeletal muscle. Consequently, we considered the possibility of a similar adaptation in the heart. With this aim, undernourished rats both in the basal state and after euglycemic hyperinsulinemic clamps were used to determine the following parameters in myocardium: glucose uptake, glucose transporter (GLUT) content, and some key components of the insulin signaling cascade. Heart membranes were prepared by subcellular fractionation in sucrose gradients. Although GLUT-4, GLUT-1, and GLUT-3 proteins and GLUT-4/1 mRNAs were reduced by undernutrition, basal and insulin-stimulated 2-deoxyglucose uptake were significantly enhanced. Phosphoinositol 3-kinase activity remained greater than control values in both conditions. The abundance of p85alpha and p85beta regulatory subunits of phosphoinositol 3-kinase was increased as was phospho-Akt during hyperinsulinemia. These changes seem to improve the insulin stimulus of GLUT-1 translocation, as its content was increased at the surface membrane. Such adaptations associated with undernutrition must be crucial to improvement of cardiac glucose uptake.
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PMID:Effects of chronic undernutrition on glucose uptake and glucose transporter proteins in rat heart. 1239 25

HL-1 cells are currently the only cardiomyocyte cell line available that continuously divides and spontaneously contracts while maintaining a differentiated cardiac phenotype. Extensive characterization using microscopic, genetic, immunohistochemical, electrophysiological, and pharmacological techniques has demonstrated how similar HL-1 cells are to primary cardiomyocytes. In the few years that HL-1 cells have been available, they have been used in a variety of model systems designed to answer important questions regarding cardiac biology at the cellular and molecular levels. Whereas HL-1 cells have been used to study normal cardiomyocyte function with regard to signaling, electrical, metabolic, and transcriptional regulation, they have also been used to address pathological conditions such as hypoxia, hyperglycemia-hyperinsulinemia, apoptosis, and ischemia-reperfusion. The availability of an immortalized, contractile cardiac cell line has provided investigators with a tool for probing the intricacies of cardiomyocyte function. In this review, we describe the culture and characterization of HL-1 cardiomyocytes as well as various model systems that have been developed using these cells to gain a better understanding of cardiac biology at the cellular and molecular levels.
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PMID:Cardiac physiology at the cellular level: use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function. 1476 71

Peripheral nerve pathology related to chronic hyperinsulinemia and hypoglycemia has yet to be fully explored. Here we conducted a systematic quantitative analysis of morphological alterations in peripheral sensory and motor nerve fibers and endoneurial microvasculature in longstanding insulinoma-carrying rats (I-rats; n=12). Age-matched normal rats (n=6) served as controls. Over the 15-month observation period, two of I-rats developed paresis of the hind limbs when their blood glucose level fell below 1.7 mmol/l. These animals showed a massive myelinated fiber loss associated with active degeneration of residual myelinated fibers and multiple endoneurial microvascular occlusions at the sciatic nerve level. The rest of the non-paretic I-rats showed a decreased density of large myelinated fibers with axonal degeneration in the peroneal nerve and an increased density of small myelinated fibers with preserved morphology in the sural nerve. This was associated with endoneurial microangiopathic changes indicative of endoneurial ischemia/hypoxia in the sciatic and peroneal nerves, and an increase in endoneurial microvascular density in the sciatic and sural nerves. In conjunction with previous data, these findings suggest that the observed increase in endoneurial microvascular density may be a compensatory response to endoneurial ischemia/hypoxia induced by chronic hyperinsulinemia in I-rats without paresis. In conclusion, the present study showed characteristic morphological alterations in peripheral sensory and motor nerve fibers associated with microangiopathy indicative of endoneurial ischemia/hypoxia in the sciatic and peroneal nerves, and provides the first evidence for the occurrence of endoneurial necrosis in the sciatic nerve, to which the hind limb paresis can be ascribed in I-rats.
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PMID:Peripheral nerve endoneurial microangiopathy and necrosis in rats with insulinoma. 1536 26

The data of modern experimental study of insulin receptors structure characteristics, the hormone effects on receptor and postreceptor molecular-cellular level, the ways hormone signal in cardiomiocites (CMC) as well as intercoupling possibility with other mediators and hormones from the point of view of probable mechanisms of hyperinsulinemia are analysed in the survey. On the basis of personal studies clinical conditions at which hyperinsulinemia manifests in patients with CAD are described. Conception is offered in accordance with which one of the reasons of "insulineresistance" at CAD can be a significant energetic CMC potential decrease as a result of myocardial metabolism remodeling in conditions of prolonged chronic ischemia, which forestalls significantly clinical manifestation of the disease.
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PMID:[Molecular-cellular effects of insulin and possible mechanisms of insulin resistance development in patients with ischemic heart disease (CAD)]. 1590 64

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

The paper reviews current data on relationships between coronary blood flow, hemodynamics, and myocardial energy metabolism during phenomena of stunned and hibernating myocardium in patients with ischemic heart disease. These data has been obtained with various modern techniques including positron emission tomography with (18)F-flourodeoxyglucose, (11)C-palmitate and (11)C-acetate. Possible association of remodeling of cardiac energetic metabolism under conditions of chronic ischemia and hyperinsulinemia in patients at various stages of ischemic heart disease is interpreted as compensatory reaction to elevation of myocardial glucose requirements.
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PMID:[Relationships between changes of coronary blood flow, energy metabolism of the myocardium, and hyperinsulinemia in patients with ischemic heart disease]. 1609 47


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