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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autonomic neuropathy of the heart associated with a primary vagal dysfunction has been frequently found in chronic diabetic patients. Little is known about the responses of hearts obtained from experimentally induced diabetic animals to cholinergic agonists. We have studied the effects of carbachol on isolated perfused working hearts from alloxan- and streptozotocin-diabetic rats as well as hearts from age-matched controls at various time points after the induction of diabetes. Carbachol produced a dose-dependent (10(-8)-10(-5) or 3 x 10(-5) M) reduction in the basal rate of left ventricular pressure development (+dP/dt) in control and diabetic rat hearts at all of the time points studied. There was no change in the sensitivity of diabetic rat hearts to carbachol until about 30 days after induction of diabetes. Diabetic rat hearts exhibited a reduced sensitivity to carbachol at 100 days after induction compared to age-matched control hearts. Hearts isolated from diabetic rats at 180,240 and 360 days were more sensitive to carbachol compared with control hearts. A general decrease in sensitivity of the heart to carbachol was observed in both control and diabetic rats at 360 days. The results demonstrate that the sensitivity of diabetic myocardium changes as the disease state progresses. The alterations could be due to the development of an autonomic neuropathy in the heart.
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PMID:Effect of alloxan- and streptozotocin-induced diabetes on isolated rat heart responsiveness to carbachol. 634 41

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.
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PMID:Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. 634 59

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.
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PMID:Altered sensitivity of chronic diabetic rat heart to calcium. 636 27

The effects of L-carnitine administration on the severity of diabetes were investigated. Serum glucose, free fatty acids (FFA), triglycerides, and ketones from diabetic and normal rats injected for 2 weeks with 3 g/kg/d of either L-carnitine or saline were assayed. Hearts were analyzed for carnitine and long-chain acyl coenzyme A. L-carnitine treatment to diabetic rats significantly reduced serum glucose, FFA, triglycerides, and ketones. In nondiabetic rats, carnitine increased serum ketones while FFA and triglycerides were decreased. L-carnitine treatment to diabetic rats prevented a decrease in myocardial total carnitine content. Long-chain acyl carnitine increased while long-chain acyl coenzyme A decreased. In another experiment, L-carnitine administration (750 mg/kg/d for 14 days) significantly improved the recovery of cardiac output after 60, 90, and 120 minutes of ischemia in diabetic perfused hearts. These results suggest that L-carnitine therapy may reduce the severity of diabetes mellitus and improve myocardial performance.
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PMID:Improvement of myocardial function in diabetic rats after treatment with L-carnitine. 670 20

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2-5.0 microM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62-73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations less than 7 microM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.
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PMID:The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines. 688 99

To explore the effects of diabetes on myocardial function and metabolism we injected male rats with streptozotocin and studied their hearts 8 weeks later. Blood sugar levels in the treated rats were about 600 mg/100 ml. Body and heart growth rates were diminished. When studied in an isolated working rat heart apparatus using 5.5 mM glucose, hearts of diabetic animals showed diminished cardiac output and stroke work at high filling pressures. There also were significant depressions in peak left ventricular systolic pressure, peak aortic flow rate, maximum negative dP/dt, myocardial oxygen extraction, myocardial lactate production, and effluent lactate:pyruvate ratios. Myocardial glycogen stores, calculated glycogen utilization, and pyruvate production were increased in hearts of diabetics, and myocardial oxygen consumption was the same as in control hearts. The end-diastolic pressure-volume relationship was shifted to the right in hearts of diabetics. Most of the abnormalities observed in hearts of diabetic rats persisted when insulin and 15 mM glucose were included in the perfusion medium. Hearts from young rats or from age-matched food-restricted rats with heart weights similar to those of diabetics did not show depressed function or a pressure-volume shift. Our findings indicate that streptozotocin diabetes in rats results in abnormal myocardial performance. This is not due to restrictions in coronary flow or myocardial oxygenation and is not correctable by the provision of high glucose plus insulin in the perfusion medium.
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PMID:The effect of diabetes on performance and metabolism of rat hearts. 700 45

In diabetes a primary myocardial defect occurs that is characterized by decreases in systolic pressure and cardiac output. The present study investigates whether diabetes causes a decreased maximum tension-generating ability, decreased Ca2+ sensitivity of myofilaments, or no change in cardiac myofilament contractile properties at pH 7.0 and 6.6. Hearts from Wistar rats were excised and mechanically disrupted 6-10 wk after injection of streptozotocin. The resulting myocyte-size preparations of skinned myocardium were used to determine the steady-state tension-negative, log molar Ca2+ concentration (pCa) relation. Maximum tension was unchanged, and the pCa of half-maximum tension generation was 0.14 pCa units lower than control for skinned myocytes from diabetic rats at pH 7.0. A significantly lower than normal maximum tension was observed at pH 6.6 for cardiac myocytes from diabetic rats. Increased expression of beta-myosin heavy chain (MHC) occurred in hearts from diabetic rats. Two troponin T (TnT) isoforms in myocardium of adult rats were identified by Western blots. The ratio of the two TnT isoforms were altered in diabetes. Changes in cardiac MHC and TnT expression may contribute to the observed decrease in Ca2+ sensitivity of myofilaments at pH 7.0 and decreased maximum tension-generating ability at pH 6.6 in diabetes.
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PMID:Effects of diabetes on isometric tension as a function of [Ca2+] and pH in rat skinned cardiac myocytes. 750 62

The mechanisms underlying the teratogenicity of maternal copper deficiency, zinc deficiency, and diabetes are largely unknown. Here we investigated whether these insults are associated with altered patterns of cell death in gestation day (GD) 11.0 rat embryos. Four weeks prior to mating, rats in the copper-deficient group (CuD) were fed a copper-deficient diet supplemented with the chelator, triethylenetetramine, to facilitate the depletion of tissue copper stores. Rats in this group were switched to a triethylenetetramine-free copper-deficient diet 1 week prior to mating. Dams in the diabetic and control groups were fed a control (8 micrograms copper, 25 micrograms zinc/g) diet throughout the study. On GD 3.0, one subset of the control dams was assigned to the zinc-deficient group (ZnD) and fed a zinc-deficient diet. A second subset of control dams was assigned to a restricted fed group and fed the control diet in quantities consumed by the zinc-deficient dams. Litters were taken by cesarean section on GD 11.0. Embryos were examined for gross morphology and assessed for patterns of cell death using Nile blue sulfate. Embryos from the CuD dams were characterized by edematous hindbrain. Embryos from the diabetic group were characterized by delayed development. Altered patterns of cell death were only detected in embryos from the ZnD dams. Within the ZnD group, embryos were either characterized by small size, edematous head region, and control patterns of cell death, or normal size, normal morphology, and increased cell death. These different patterns of morphology and cell death in the embryos of ZnD dams were associated with different patterns of maternal food intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maternal zinc deficiency, but not copper deficiency or diabetes, results in increased embryonic cell death in the rat: implications for mechanisms underlying abnormal development. 766 Mar 26

Although myocardial triacylglycerol may be a potentially important source of fatty acids for beta-oxidation in diabetes, few studies have measured triacylglycerol turnover directly in hearts from diabetic animals. In this study, myocardial triacylglycerol turnover was directly measured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 mM [14C]palmitate and 11 mM glucose for 1 h (pulse) to label the endogenous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM glucose +/- 1.2 mM [3H]palmitate. During the chase, both 14CO2 and 3H2O production (measures of endogenous and exogenous fatty acid oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [14C(U),5-3H]glucose +/- unlabeled palmitate was present during the chase. Both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 +/- 4.6 vs. 33.7 +/- 4.1 mumol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis was increased, although endogenous [14C]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP production. The majority of fatty acids derived from triacylglycerol lipolysis were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [14C]palmitate oxidation rates were significantly increased in diabetic rat hearts, compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Triacylglycerol turnover in isolated working hearts of acutely diabetic rats. 788 74

To test whether diabetes associated alterations in copper metabolism contribute to diabetes-induced teratogenicity in rats, pregnancy outcome was compared between diabetic and nondiabetic rats fed either a copper adequate (12 micrograms/g diet) or low copper diet (1 microgram/g diet). The dietary regimen was begun two weeks prior to mating and continued throughout pregnancy. To facilitate the reduction of maternal copper stores in the low copper groups, the low copper diet was supplemented with a copper chelator, triethylenetetraamine, at 1% for one week; the chelator was removed from the diet one week prior to mating. Pregnancy was terminated on gestation day 20. Maternal and fetal tissues were assessed for copper concentrations, the activities of the cuproenzymes copper, zinc superoxide dismutase and ceruloplasmin, and the copper binding protein metallothionein. Dams fed the low copper diet had low tissue copper concentrations, and low plasma ceruloplasmin and erythrocyte superoxide dismutase activities compared to copper-adequate dams. Fetuses in the low copper groups were characterized by low liver copper concentrations. Gross structural and skeletal anomalies were only observed in the diabetic groups; maternal copper intake did not influence the frequency of these anomalies. However, fetuses in the low-copper nondiabetic group, and both diabetic groups, were characterized by low liver copper, zinc superoxide dismutase activity suggesting that fetal copper metabolism was influenced by both copper intake and diabetes.
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PMID:Effect of maternal diabetes and dietary copper on fetal development in rats. 811 9


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