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

Diabetes was induced in pregnant rats by administration of streptozotocin and the changes of the feto-placental unit were investigated. Dead fetuses were found in 12% of the untreated diabetic animals. In comparison to the controls, the fetal weights were significantly smaller and placental weights greater in diabetic animals. The changes were clearly characterized by the ratio fetal placental weight. Edema and cystic degeneration were characteristic of insulin treated diabetic placentas while fibrosis and ischemia were observed mainly in untreated animals. Insulin treatment resulted in hemorrhages and necrosis in the placenta of normal pregnant rats; the change is ascribed to hypoglycaemia.
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PMID:Clinical and morphological studies in streptozotocin diabetic pregnant rats. 13 71

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

Insulin was administered to two patients whose diminished myocardial contractility made it difficult to terminate cardiopulmonary bypass. In both instances, bypass was successfully terminated shortly after the insulin injection. These clinical observations led to experiments under the controlled conditions provided by the isolated, working rat heart preparation. The recovery of contractility after 30 minutes of severe ischemia was assessed in all 11 control and 11 insulin-treated hearts. Myocardial performance, as judged by the product of heart rate and peak systolic blood pressure, was significantly greater in the insulin-treated hearts. These clinical observations and experimental findings suggest the need for more extensive study of the potential value of insulin in treating depressed contractility after prolonged myocardial ischemia.
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PMID:Insulin therapy for depressed myocardial contractility after prolonged ischemia. 66 28

Insulin and insulin-like growth factors I and II (IGF-I and IGF-II) have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action in the brain are unknown. Since central neurons are particularly vulnerable to hypoglycemia that results from ischemia or other insults, we tested the hypothesis that growth factors can protect central neurons against hypoglycemic damage in vitro. IGF-I and IGF-II (3-100 ng/ml) each prevented glucose deprivation-induced neuronal damage in a dose-dependent manner in rat hippocampal and septal cell cultures. High concentrations of insulin (greater than 1 microgram/ml) also protected neurons against hypoglycemic damage. Epidermal growth factor did not protect against hypoglycemic damage. Both IGFs and insulin were effective when administered 24 hr before or immediately following the onset of glucose deprivation. Direct measurements of intraneuronal calcium levels and manipulations of calcium influx demonstrated that calcium influx and sustained elevations in intraneuronal calcium levels mediated the hypoglycemic damage. IGF-I and IGF-II each prevented the hypoglycemia-induced elevations of intraneuronal free calcium. Studies with excitatory amino acid receptor antagonists and calcium channel blockers indicated that NMDA receptors did, and L-type calcium channels did not, play a major role in hypoglycemic damage. Taken together, these findings indicate that IGFs can stabilize neuronal calcium homeostasis and thereby protect against hypoglycemic damage.
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PMID:IGF-I and IGF-II protect cultured hippocampal and septal neurons against calcium-mediated hypoglycemic damage. 131 98

Insulin-like growth factors (IGFs) are important stimulators of proliferation and differentiation of cultured myoblasts. It has previously been shown that IGF-I is induced during muscle regeneration in rodents, however, little is known about the expression of IGF-II. Therefore, two in vivo models were used to analyze IGF-II mRNA expression during skeletal muscle regeneration in the rat: injection of the snake venom notexin and induction of ischemia. During the regeneration process the levels of both IGF-I and IGF-II mRNA were transiently induced, as analyzed by solution hybridization. Both IGF-I-like immunoreactivity and IGF-II-like immunoreactivity were found to be present during muscle regeneration. In a time course study, induction of IGF-II was preceded by IGF-I, both at the mRNA and protein levels. Using alpha- and beta-actin as markers for different stages of skeletal muscle differentiation, together with the immunohistochemistry data, it is concluded that the expression of IGF-I and IGF-II occurs at different differentiation stages, and that IGF-II appears concomitant to the formation of myotubes. These results suggest that each IGF has a distinct role during the differentiation of muscle cells.
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PMID:Activation of insulin-like growth factor II expression during skeletal muscle regeneration in the rat: correlation with myotube formation. 140 1

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.
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PMID:Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage. 154 41

Ischemic hepatitis is not an uncommon complication of reversible severe hypotension or cardiac failure. The prognosis usually is determined by the cause of the initial hypotension or cardiac failure, rather than the subsequent hepatic dysfunction. We report a retrospective analysis of nine patients with ischemic hepatitis in which previously unreported clinical and biochemical abnormalities are noted. The clinical and biochemical course of the patients were reviewed until recovery or death from ischemic hepatitis. All the patients had a rapid striking elevation of aspartate aminotransferase, and lactic dehydrogenase, with an equally rapid resolution of these parameters. Abnormal serum glucose levels occurred in six patients (none of whom had a prior carbohydrate intolerance). Insulin therapy was given to three patients for a limited period. Renal impairment was manifest in all nine patients, and it resolved spontaneously within 10 days. Altered mental status was detected in six patients; the changes reverted to normal within 7 days of their onset. A preexisting anemia (hemoglobin less than 11.0 g/dl) was noted on admission in four patients, and it did not appear to potentiate the manifestations of the hepatic ischemia. We conclude that ischemic hepatitis should be anticipated in all patients with a recent history of systemic hypotension. It should be considered in the differential diagnosis of patients with unexplained hepatitis; the early massive rise in lactic dehydrogenase, the rapid fall in transaminases, and the early mild/moderate renal failure strongly suggest ischemic hepatitis. Patients with ischemic hepatitis can manifest reversible renal failure, mental confusion, and hyperglycemia which may require insulin for its control.
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PMID:Ischemic hepatitis: widening horizons. 848 Jul 56

Prostaglandin E1/I2 and insulin receptors of human erythrocyte and platelet are capable of modulating each other's activity. This modulation of the receptor activity and number in one system by a second receptor system in human platelet and erythrocyte seems to be beneficial. Insulin increases the PGE1 binding to platelets and thereby enhances the platelet antiaggregatory action of prostaglandin by increasing cyclic AMP levels. Similarly, PGE1 increases insulin binding to human erythrocyte, and thereby reduces the optimum concentration of insulin for a maximal reduction in membrane microviscosity. During ischemia the reduced response of platelets to the inhibitory effect of PGE1 or PGI2 relates to the impaired PGE1/I2 receptor activity. Treatment of these platelets with insulin at physiological concentrations can normalise the PGE1/I2 receptor activity. This review focuses on the relationship between the two receptor systems in human blood cells.
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PMID:Interaction of receptors for prostaglandin E1/prostacyclin and insulin in human erythrocytes and platelets. 165 91

Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-min episode of postischemic hypotension. Insulin reduced pan-necrosis in addition to selective neuronal necrosis: The infarction rate was reduced in the cerebral cortex, thalamus, and substantia nigra pars reticulata. Normoglycemic ischemia produced only selective neuronal necrosis, but a beneficial effect on structural damage was also seen. The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis. Possible direct CNS mechanisms of action include an effect on central insulin receptors mediating inhibitory neuromodulation, an effect on central neurotransmitters, or a growth factor effect of insulin.
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PMID:Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. 193 78

Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period.
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PMID:Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin. 200 13


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