Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a major risk factor for cardiovascular disease. However, a direct link between these two states is difficult to establish, since obesity frequently occurs with other disease states such as diabetes, hypertension and atherosclerosis. Clinical studies have clearly shown that uncorrected obesity is associated with cardiac hypertrophy and compromised ventricular function. A number of rodent models of obesity have been studied in terms of cardiovascular adaptations. Cardiac function of the obese Zucker rat appears to be normal at a younger age. Only after several months is depression in cardiac function discernable. These animals are mildly hypertensive, but do not exhibit the characteristic increase in cardiac output associated with human obesity. A unique characteristic of JCR:LA-cp rat is that they develop atherosclerotic and myocardial lesions. Hearts from these animals will maintain normal function when perfused with physiological levels of calcium. At higher calcium concentrations, however, mechanical function becomes impaired. Dietary-induced obese rats exhibit many of the hemodynamic alterations associated with human obesity, but there is no evidence to-date that these animals will develop severe cardiac depression. Short-term weight reduction apparently has beneficial cardiovascular effects, but weight cycling may be harmful. Given the widespread occurrence of obesity, further studies are warranted to characterize the cardiac manifestations of this condition.
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PMID:Cardiovascular abnormalities associated with human and rodent obesity. 143 63

Diabetics suffer from an increased incidence of myocardial infarction and are less likely to survive an ischemic insult. Since L-propionylcarnitine (LPC) has been shown to protect against ischemic/reperfusion injury, we hypothesized that LPC may be of even greater benefit to the diabetic heart. Diabetes was induced by i.v. streptozotocin, 60 mg/kg; duration: 12 wks. The chronic effect of LPC was determined by daily i.p. injections (100 mg/kg) for 8 wks. The acute effects of LPC were determined by adding it to the perfusion medium (5 mM) of control and diabetic hearts. Initial cardiac contractile performance of isolated perfused working hearts was assessed by varying left atrial filling pressure. Hearts were then subjected to 90 min of low flow global ischemia followed by 30 min reperfusion. Chronic LPC treatment had no effect on initial cardiac performance in either control or diabetic hearts. Acute addition of LPC to the perfusion medium enhanced pump performance of control hearts, but had no effect in diabetic hearts. Both acute and chronic LPC significantly improved the ability of control and diabetic hearts to recover cardiac contractile performance after ischemia and reperfusion, however, chronic treatment was more effective in diabetic hearts.
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PMID:Protection of the ischemic diabetic heart by L-propionylcarnitine therapy. 148 Jan 41

This study determined whether exercise training in rats would prevent the accumulation of lipids and depressed glucose utilization found in hearts from diabetic rats. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Training of diabetic rats had no effect on glycemic control but decreased plasma lipids. In vivo myocardial long-chain acylcarnitine, acyl-CoA, and high-energy phosphate levels were similar in sedentary control, sedentary diabetic, and trained diabetic groups. The levels of myocardial triacylglycerol were similar in sedentary control and diabetic rats but decreased in trained diabetic rats. Hearts were perfused with buffer containing diabetic concentrations of glucose (22 mM) and palmitate (1.2 mM). D-[U-14C] glucose oxidation rates (14CO2 production) were depressed in hearts from sedentary diabetic rats relative to sedentary control rats. Hearts from trained diabetic rats exhibited increased glucose oxidation relative to those of sedentary diabetic rats, but this improvement was below that of the sedentary control rats. [9,10(-3)H]palmitate oxidation rates (3H2O production) were identical in all three groups. These findings suggest that exercise training resulted in a partial normalization of myocardial glucose utilization in diabetic rats.
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PMID:Metabolic effects of treadmill exercise training on the diabetic heart. 150 79

Hearts isolated from 1-yr-old non-insulin-dependent diabetic rats exhibited reduced responsiveness to the beta-adrenergic agonist isoproterenol. Over a concentration range of 3 x 10(-9) to 10(-7) M, isoproterenol-mediated stimulation in the rate of left ventricular pressure decline, a measure of myocardial relaxation, and the rate of left ventricular pressure rise, a measure of myocardial contractility, were significantly depressed in the diabetic hearts. To clarify the basis for this defect, individual steps involved in the actions of the beta-adrenergic agonists were examined. Dihydroalprenolol binding assays revealed that neither beta-adrenergic receptor number nor binding affinity was affected by the diabetic condition. Also unaffected by diabetes was isoproterenol-mediated stimulation of adenylate cyclase activity, myocyte accumulation of adenosine 3',5'-cyclic monophosphate (cAMP), or the increase in cAMP-dependent protein kinase activity ratio. However, it was found that both in the presence and absence of cAMP-dependent protein kinase, activity of the sarcolemmal calcium transporter was significantly depressed in the diabetic heart. Also attenuated was protein kinase-induced enhancement of sarcoplasmic reticular calcium transport. The likelihood that these abnormalities contribute to alterations in calcium homeostasis and myocardial contractile function is discussed.
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PMID:Defective response to cAMP-dependent protein kinase in non-insulin-dependent diabetic heart. 165 26

The purpose of this study was to examine the protective activity of a low concentration of nifedipine (3 x 10(-8) M) against global myocardial ischemic injury in isolated perfused hearts from streptozotocin (STZ) diabetic rats (DR) as compared with control rats (CR). Hearts were subjected to 45-min global ischemia followed by 45-min reperfusion. During ischemia, the period of time until onset of the ischemic contracture was significantly longer in hearts from DR than in hearts from CR (20.3 +/- 1.0 and 15.5 +/- 0.5 min, p less than 0.05). The degree of the ischemic contracture was similar in both types of hearts. During reperfusion, a significantly smaller recovery of left ventricular pressure (LVP) was observed as was a tendency for postischemic coronary flow (CF) to be lower in hearts from DR than in those from CR. After pretreatment with nifedipine, the time of onset of the ischemic contracture was significantly more delayed in hearts from DR than in those from CR: from 20.3 +/- 1.0 to 28.1 +/- 1.2 min (p less than 0.05) and from 15.5 +/- 0.6 to 18.1 +/- 0.9 min (p less than 0.05), respectively. In addition, the degree of the ischemic contracture was reduced (45.3%) in hearts from DR but not in those from CR. During reperfusion, the CF was increased only in hearts from DR. No beneficial effects on functional recovery of LVP were observed in either type of hearts, although recovery tended to be better in diabetic hearts. Nifedipine in a low concentration appears to be more effective against myocardial ischemic injury in diabetes, resulting in an improvement in postischemic CF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nifedipine on global myocardial ischemic injury in hearts from diabetic and age-matched control rats. 172 31

Biochemical alterations in the hearts of non-diabetic and 5 weeks of streptozotocin-induced diabetic rats following isoproterenol (ISO) administration were compared. Serum lactate dehydrogenase (LDH) and myocardial adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycogen were used as indices of myocardial injury. Hearts from diabetic rats (blood glucose greater than 350 mg/dl), before ISO administration, had normal lactate levels but significantly low high-energy phosphate (HEP) levels and high glycogen levels in comparison to non-diabetic rats. No difference was observed in serum LDH levels between these two groups. ISO administration to non-diabetic rats caused myocardial necrosis as evidenced by a significant depletion of myocardial glycogen and HEPs along with significant myocardial lactate accumulation and an increase in serum LDH. However, the hearts from diabetic rats failed to show any significant HEP depletion, accumulation of lactate and leakage of LDH into serum following ISO-administration, though myocardial glycogen level was significantly lowered. These observations, in conjunction with earlier reports, point to the hypothesis that, in diabetes, there are certain alterations in the sarcolemma which hamper the process by which ISO causes myocardial necrosis.
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PMID:Isoproterenol fails to produce myocardial necrosis in streptozotocin-induced diabetic rats. 183 21

1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.
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PMID:Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats. 247 2

1. Hearts of diabetic rats gradually accumulate glycogen, although the activities of glycogen synthase and glycogen phosphorylase are altered in favor of a depletion of glycogen. 2. Phosphorylase in diabetic hearts has been reported to be even more activated in response to adrenaline than controls. 3. The situation is further complicated by the fact that in rat heart two isoenzymes of phosphorylase are present. Therefore we have studied the properties of phosphorylases purified from diabetic rat heart in more detail. 4. This investigation revealed that compared to controls: (A) the amount of enzyme protein which could be isolated from diabetic animals is drastically lower; (B) the affinities towards glycogen and inorganic phosphate are decreased; (C) the activation by phosphorylase kinase is delayed; and (D) the inactivation by protein phosphatase-1 is accelerated. 5. We conclude that all of the reported changes in diabetes might contribute to a phosphorylase system less able to catalyze glycogen breakdown effectively.
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PMID:Activation and inactivation of glycogen phosphorylase isoenzymes purified from diabetic rat heart. 274 7

Fifteen week old male Wistar rats (n = 7) were made diabetic by intravenous injection of streptozotocin (50 mg/kg). Age-matched, untreated male Wistar rats (n = 9) served as controls. Hearts were removed after 5-6 weeks of diabetes, and the isometric developed tension (T) of isolated left ventricular papillary muscles and its first derivative (dT/dt) were measured at a frequency of 0.2 Hz. During testing, the muscles were perfused with Tyrode's solution (Ca2+ concentration was half of normal Tyrode's solution, pH 7.4, 32 degrees C, bubbled with 95% O2 and 5% CO2). In addition, the left ventricular isoenzyme pattern, which is related to myocardial energetics, was determined by pyrophosphate gel electrophoresis. There was no significant difference in isometric developed tension between diabetic and control rats (DM: 2.90 +/- 0.89 vs controls: 2.87 +/- 0.85 g/mm2, mean +/- SD), but in diabetic rats, dT/dtmax decreased significantly as compared with controls (DM: 23.5 +/- 4.2 vs controls: 31.9 +/- 7.9 g/mm2.s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7)M) and dibutyryl cyclic AMP (10(-5)M) also decreased in diabetic rats. The left ventricular myosin isoenzyme pattern shifted toward VM-3 in diabetic rats (VM-3: DM: 74.9 +/- 10.7 vs controls: 9.5 +/- 4.1%, p less than 0.001). These results indicate that diabetes influences myocardial contractility and changes cardiac energetics. Post-receptor processes may play a role in myocardial mechanical responses to catecholamines in streptozotocin-diabetic rats.
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PMID:Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats. 284 6

Diabetes produced by injection of alloxan or streptozotocin results in cardiac dysfunction in rats that is associated with lower cardiac contractile protein ATPase activity. The purpose of this investigation was to examine cardiac myosin biochemistry in the Bio-Breeding Worcester (BB/W) rat, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. Hearts from diabetic BB/W rats were studied at 1, 4, and 7 mo after the onset of diabetes and were compared with age-matched BB/W rats that were bred for resistance to diabetes. Calcium-stimulated myosin ATPase activity was significantly decreased after 4 and 7 mo of diabetes, and actin-activated myosin ATPase was significantly depressed at all time points. Differences between hearts from control and diabetic animals increased with the duration of diabetes. Closely associated with reductions in myosin ATPase activity in the diabetes was a shift in the isomyosin content from the normally predominant V1 to the V3 isoenzyme. Thus diabetes that results from genetic causes leads to depressed myosin enzymatic activity in the rat. Furthermore, since previous studies have shown that BB/W diabetic rats do not develop hypothyroidism, the present results support the view that altered thyroid function does not mediate the abnormalities in cardiac contractile proteins in diabetes.
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PMID:Abnormal cardiac biochemistry in spontaneously diabetic Bio-Breeding/Worcester rat. 293 20


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