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

Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.
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PMID:Clinical determinants of glucose homeostasis after pancreas transplantation. 868 47

Insulin induces vasodilation via stimulation of nitric oxide (NO) synthesis. This action of insulin exhibits considerable interindividual variation. We determined whether the response of blood flow to endothelium-dependent vasoactive agents correlates with that to insulin or whether other factors, such as physical fitness, limb muscularity, or vasodilatory capacity, better explain variations in insulin-stimulated blood flow. Direct measurements of the forearm blood flow response to three 2-h sequential doses of insulin (1, 2, and 5 mU/ kg.min), endothelium-dependent (acetylcholine and NG-monomethyl-L-arginine) and endothelium-independent (sodium nitroprusside) vasoactive agents, and ischemia (reactive hyperemic forearm blood flow) were performed in 22 normal subjects (age, 24 +/- 1 yr; body mass index, 22.2 +/- 0.6 kg/m2; maximal aerobic power, 40 +/- 2 mL/kg.min). The highest insulin dose increased blood flow by 111 +/- 17%. The fraction of basal blood flow inhibited by NG-monomethyl-L-arginine (NO synthesis-dependent flow) varied from 6-47%. Maximal aerobic power (r = 0.52; P < 0.02), the percentage of forearm muscle (r = 0.50; P < 0.02), and the NO synthesis-dependent flow (r = 0.42; P < 0.05), but not reactive hyperemic, acetylcholine-stimulated, or sodium nitroprusside-stimulated flow, were significantly correlated with insulin-stimulated (5 mU/kg.min) blood flow. In multiple linear regression analysis, 52% of the variation (multiple R = 0.72; P < 0.001) in insulin-stimulated blood flow was explained by NO synthesis-dependent flow (P < 0.005) and the percentage of forearm muscle (P < 0.005). We conclude that endothelial function (NO synthesis-dependent basal blood flow) and forearm muscularity are independent determinants of insulin-stimulated blood flow.
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PMID:Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects. 895 24

Many clinical and laboratory studies suggest that an increase in glucose uptake and metabolism by ischemic myocardium helps protect myocardial cells from irreversible injury. We have examined whether increased sarcolemmal abundance of cardiomyocyte glucose transporters plays a role in this adaptive response. We have shown that acute myocardial ischemia in perfused rat hearts results in increased sarcolemmal abundance of the major glucose transporter, GLUT4, by causing translocation of GLUT4 molecules from an intracellular compartment to the sarcolemma. In nonischemic control hearts only 18 +/- 2.8% of GLUT4 molecules were on the sarcolemma whereas in ischemic hearts this increased to 41 +/- 9.3%. Insulin also caused translocation of GLUT4 molecules to the sarcolemma, and resulted in 61 +/- 2.6% of GLUT4 molecules on the sarcolemma. The combination of ischemia and insulin did not result in additive increases in sarcolemmal GLUT4 abundance. In more persistent or chronic ischemia, the other major myocardial glucose transporter, GLUT1, appears to play an important role. The mRNA for this transporter, which is constitutively expressed on cardiomyocyte sarcolemma, was increased 2.0-fold in regions of hibernating myocardium in humans with coronary heart disease as well as in persistently hypoxic rat neonatal cardiomyocytes in primary culture. In neither of these conditions was GLUT4 mRNA expression increased. Thus, acute myocardial ischemia increases sarcolemmal glucose transporter abundance mainly by translocating previously synthesized GLUT4 molecules from an intracellular compartment, whereas more chronic ischemia also increases GLUT1 abundance via enhanced mRNA expression. Increased GLUT1 and GLUT4 abundance may participate in the augmented glucose uptake of ischemic myocardium and therefore may help protect ischemic myocardium from irreversible injury.
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PMID:Increased sarcolemmal glucose transporter abundance in myocardial ischemia. 929 58

We tested the hypothesis that low-flow ischemia increases glucose uptake and reduces insulin responsiveness. Working hearts from fasted rats were perfused with buffer containing glucose alone or glucose plus a second substrate (lactate, octanoate, or beta-hydroxybutyrate). Rates of glucose uptake were measured by 3H2O production from [2-3H]glucose. After 15 min of perfusion at a physiological workload, hearts were subjected to low-flow ischemia for 45 min, after which they were returned to control conditions for another 30 min. Insulin (1 mU/ml) was added before, during, or after the ischemic period. Cardiac power decreased by 70% with ischemia and returned to preischemic values on reperfusion in all groups. Low-flow ischemia increased lactate production, but the rate of glucose uptake during ischemia increased only when a second substrate was present. Hearts remained insulin responsive under all conditions. Insulin doubled glucose uptake when added under control conditions, during low-flow ischemia, and at the onset of the postischemic period. Insulin also increased net glycogen synthesis in postischemic hearts perfused with glucose and a second substrate. Thus insulin stimulates glucose uptake in normal and ischemic hearts of fasted rats, whereas ischemia stimulates glucose uptake only in the presence of a cosubstrate. The results are consistent with two separate intracellular signaling pathways for hexose transport, one that is sensitive to the metabolic requirements of the heart and another that is sensitive to insulin.
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PMID:Effects of insulin on glucose uptake by rat hearts during and after coronary flow reduction. 937 50

Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin-dependent) diabetes mellitus can have adverse consequences, including increased neurologic ischemia, delayed wound healing and an increased infection rate. Poor glycemic control can also affect the outcome of the primary illness. If possible, hospitalized diabetic patients should continue their previous antihyperglycemic treatment regimen. Decreased physical activity and the stress of illness often lead to hyperglycemia in hospitalized patients with type 2 diabetes. When indicated, insulin is given either as a supplement to usual therapy or as a temporary substitute. The overall benefit of the traditional sliding-scale insulin regimen has been questioned. Insulin supplementation given according to an algorithm may be a logical alternative. Any antihyperglycemic regimen should be administered and monitored in a manner coincident with the intake of food or other sources of calories. Factors that can alter glycemic control acutely, including specific medical conditions and medications, should be identified and anticipated.
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PMID:Management of hospitalized patients with type 2 diabetes mellitus. 951 54

Pig islets are considered the best alternative to human islets in the treatment of insulin-dependent diabetes. Pigs could represent a potential islet donor for xenotransplantation in humans because of the close similarity between human and porcine insulin and the theoretically unlimited availability of porcine pancreas. From November 1991 to January 1997 we performed 221 pig islet isolations from 3 pig sources: group 1: minipigs (age 9-18 months) and white pigs (3-8 months), group 2: large white pigs (5-8 months), group 3: large white pigs (12-24 months). Islets were isolated according to a semi-automated method using enzymatic digestion and purification through discontinuous Euro-Ficoll gradients. The pancreases were surgically removed in our laboratory for group 1, while pancreases from groups 2 and 3 were removed at the slaughterhouse with an average warm ischemia time of 15 minutes. In vitro islet function was assessed by static incubations and perifusions, and in vivo islet function by transplantation under the kidney capsule of nude diabetic mice. The results were as follows: [table: see text] Insulin secretion increased twofold after in vitro glucose stimulation. We obtained restoration of euglycemia in diabetic mice which survived > 3 months after the graft and returned to diabetes after nephrectomy. This study shows that our isolated pig islets are viable and functional in vitro and in vivo after transplantation.
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PMID:[Isolation of the pig islets of Langerhans: evaluation of in vitro and in vivo function]. 965 22

Intensive efforts are presently directed toward developing pharmacologic therapy to protect the ischemic brain. Preclinical data from animal models indicate that insulin, already available for human use, may reduce damage in both global and focal ischemia. Two kinds of mechanisms may be involved: one in which insulin interacts directly with brain tissue and one in which insulin acts indirectly by reducing peripheral blood glucose levels. Animal data indicate that part of the former, direct mechanism is mediated by insulin-like growth factor-1 receptors. The direct effect appears to predominate in global ischemia. In focal ischemia, unlike global ischemia, the effect of insulin is predominantly via peripheral hypoglycemia, because neuroprotection is largely annulled by co-administration of glucose. The two clinical counterparts of global and focal ischemic models are, respectively, cardiac arrest encephalopathy and focal ischemic stroke. Insulin use in both of these clinical situations could be evaluated in clinical trials that attempt to reduce ischemic brain damage, because insulin has a long and safe history of human use in diabetes treatment.
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PMID:Insulin, blood glucose levels, and ischemic brain damage. 974 32

Insulin improves myocardial contractile function during moderate ischemia, but the mechanism is unknown. To determine effects of insulin on myocardial oxygen utilization efficiency (O2UE) and energetics, regional left coronary perfusion pressure (CPP) was lowered sequentially from 100 to 60, 50, and 40 mmHg in 24 anesthetized, open-chest dogs. Regional power index (PI), myocardial oxygen consumption (MVO2), and O2UE index (PI/MVO2) were determined in untreated and insulin treated (4 U/min, i.v.) hearts. Biopsies were obtained from six untreated and six insulin-treated hearts at CPP=40 mmHg for determining high energy phosphates and the cytosolic phosphorylation potential. Measurements were compared with data from normal, untreated myocardium (n=11). MVO2 fell (P<0.05) in all hearts as CPP was lowered to 40 mmHg, and was unaffected by insulin treatment. PI decreased 32 and 75% in untreated hearts at CPP=50 and 40 mmHg, respectively (P<0.05). In insulin treated hearts, PI was not significantly depressed at CPP>40 mmHg, and fell only 26% at CPP=40 mmHg. O2UE increased (P<0.05) in all hearts at CPP=60 mmHg. In insulin treated hearts, O2UE was greater (P<0.05) at CPP=50 and 40 mmHg than at CPP=100 mmHg, and greater (P<0.05) than in untreated hearts at CPP=40 mmHg. Reducing CPP to 40 mmHg produced similar metabolic changes in all hearts. Compared to normal myocardium, ATP content of untreated and treated hearts was unchanged, creatine phosphate content decreased 21 and 14%, creatine content increased 24 and 30%, inorganic phosphate concentration increased 108 and 140%, and phosphorylation potential decreased 80 and 77%. We conclude that insulin markedly improves PI and O2UE without altering cytosolic energetics during moderate myocardial ischemia.
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PMID:Insulin improves cardiac contractile function and oxygen utilization efficiency during moderate ischemia without compromising myocardial energetics. 979 56

Feet lesions are the most important cause of diabetic's consultation in general surgery. A retrospective study was conducted in Ouagadougou National Teaching Hospital, in order to analyse epidemiology, clinic, and evolutive aspects of this affection. In the same period, 222 cases of diabetes mellitus were admitted in general surgery and internal medicine. We noticed 42 cases of feet lesions. The mean age of patients was 53 years. Anterior knowledge of diabetes has not been a factor of early consultation. Consultation mean delay was a month. In 28 cases, feet lesions were 4 or 5 Wagner grade. The role of ischemia and neuropathy have not been evaluated, but sepsis was highly determinant factor. Insulin has been used in 83.3% of cases. Amputation concerned 19 patients. Mean length of hospital stay was 16.6 days and mortality rate was 38.1%. Prevention of complications can be much more effective if it is applied as a part of global approach to diabetes mellitus management.
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PMID:[Management of the diabetic foot, apropos of 42 cases at the Ougadougou University Hospital Center]. 982 68

The authors tested the hypothesis that ischemia stimulates glucose uptake in rat heart independent of the insulin signaling pathway and independent of endogenous catecholamines. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/l, 0.05 muCi/ml) and Na-oleate (0.4 mmol/l) with or without the phosphatidylinositol 3-kinase inhibitor wortmannin (3 mumol/l). Insulin (1 mU/ml) was added to the perfusate in the middle of the experiments or the hearts were subjected to 30 min of low-flow ischemia (75% reduction in coronary flow) followed by 15 min of reperfusion. In a separate group, hearts were subjected to ischemia and reperfusion in the presence of propranolol (10 mumol/l) plus phentolamine (10 mumol/l). Cardiac power was stable but decreased (-75%) during ischemia. Both insulin and ischemia increased glucose uptake (P < 0.01). Glucose uptake returned to pre-ischemic values during reperfusion. Wortmannin completely inhibited insulin-stimulated glucose uptake and glycogen synthesis, but did not affect the ischemia-stimulated glucose uptake or glycogen resynthesis during reperfusion. Full adrenergic blockade did not abolish the ischemia-stimulated glucose uptake. The authors conclude that: (1) insulin and ischemia increase glucose uptake through different mechanisms; (2) ischemia-stimulated glucose uptake is not catecholamine mediated: and (3) glycogen resynthesis during reperfusion is independent of PI3-K.
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PMID:Ischemia-stimulated glucose uptake does not require catecholamines in rat heart. 1009 55


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