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)

The aim of this study was to test the hypothesis that the antiadrenergic action of adenosine is reduced in diabetes. This was determined by evaluating the effect of experimental diabetes mellitus on the in vivo myocardial antiadrenergic action of cyclopentyladenosine, and adenosine A1-receptor agonist. Changes in heart rate and ventricular performance in response to infusion of dobutamine, a beta 1-adrenergic agonist, were determined in the absence and presence of cyclopentyladenosine, in anesthetized, 10- to 12-week male diabetic (60 mg/kg streptozotocin), insulin-treated diabetic and control rats. Intravenous dobutamine (16 micrograms/kg) increased +dP/dtmax and -dP/dtmax in control rats from 7,706 +/- 553 and 5,449 +/- 403 mmHg/s (1 mmHg = 133.3 Pa) to 19,170 +/- 465 and 8,855 +/- 317 mmHg/s, respectively. In diabetic rats dobutamine increased +dP/dtmax and -dP/dtmax from 5,733 +/- 541 and 4,016 +/- 426 to 15,015 +/- 1,521 and 7,039 +/- 809 mmHg/s, respectively. Cyclopentyladenosine significantly attenuated dobutamine-stimulated increases in +dP/dtmax and -dP/dtmax in both control and diabetic rats in a dose-dependent (0.1-3.0 micrograms/kg) manner. Cyclopentyladenosine potency to attenuate dobutamine-enhanced +dP/dtmax was reduced significantly (p < 0.05) in diabetic rats compared with controls (ID50, 1.07 vs. 0.59 micrograms/kg, respectively) with no change in efficacy. The magnitude of cyclopentyladenosine inhibition of dobutamine-enhanced -dP/dtmax was greater in control than diabetic rats (81 vs. 54%, respectively), but ID50 values were not different. Insulin treatment of diabetic rats prevented the observed changes. These data suggest that the antiadrenergic action of adenosine is compromised in diabetes and that this may contribute to the development of diabetic cardiomyopathy.
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PMID:The antiadrenergic effect of cyclopentyladenosine on myocardial contractility is reduced in vivo in diabetic rats. 788 91

We examined the characteristics of the action potentials of single ventricular myocytes obtained from the hearts of rats with chronically-induced diabetes. Male Wistar rats were made diabetic by injecting streptozotocin (65 mg/kg) and 30-32 weeks later the hearts were excised and used for an electrophysiological study. Action potentials were recorded from isolated right ventricular myocytes by an electrode fabricated for patch clamp in the whole-cell recording configuration. The action potential durations (APDs) of steady state chronic diabetic rat myocytes were longer than those of age-matched normal rat myocytes at all levels of repolarization (APD25, APD50, APD75, and APD90). As the stimulation frequency was increased (0.2-2 Hz), the APDs were lengthened in both diabetic and normal rats, and the difference of APDs between the groups was greater when the stimulation frequency was higher. When we examined alterations of APDs under conditions of train stimulation (2Hz, 20 stimuli), (1) the APDs in both groups were prolonged, and (2) the degree of prolongation of APD was significantly greater and the rate of APD prolongation was significantly faster in myocytes from the diabetic rats. The prolongation of APD in these heart cells is probably secondary to alteration of the transient outward current Ito, and sheds light on repolarization abnormality in cases of diabetic cardiomyopathy.
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PMID:Rate-dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30-32 weeks. 788 52

The effects of severe, chronic diabetes mellitus and of immediate or delayed insulin replacement on the different components of the myocardium and cardiocytes were quantified and correlated. A significant decrease in cardiocyte cross-sectional area occurred during the first 12 weeks of diabetes and then stabilized. This was accompanied by decreases in the relative volume densities (RVDs) of myofibrils and mitochondria, resulting in absolute loss of more than 40% of each of these cellular components after 26 weeks of diabetes. Interstitial and perivascular deposition of extracellular matrix produced a tripling of its RVD in the myocardium over 26 weeks of diabetes at the expense of both cardiocytes and capillaries. Capillary density and diameter also exhibited progressive decreases of more than 20% over 26 weeks of diabetes. Insulin treatment which maintained euglycemia and restored normal growth prevented this structural pathology when begun three days after induction of diabetes. When delayed for 12 weeks, insulin reversed the changes in cardiocyte and capillary RVD, and in capillary diameter within 6 weeks, ultrastructural changes within 12 weeks, and cardiocyte cross-sectional area after 26 weeks. However, even after 26 weeks of treatment, the extracellular matrix remained more than twice that observed in nondiabetic animals, with a consequent decrease in the number of capillaries per unit volume of tissue. This study demonstrates that diabetes produces a progressive, marked disorganization of the myocardium which can be prevented, but only selectively reversed, by insulin treatment. These structural changes are relevant to the functional changes which occur in diabetic cardiomyopathy.
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PMID:Quantitative analysis of myocardial structure in insulin-dependent diabetes mellitus: effects of immediate and delayed insulin replacement. 817 Oct 52

The functional and morphological changes in myocardium of diabetic patients is caused by diabetic macroangiopathy, diabetic microangiopathy, autonomic neuropathy and metabolic disorders. Mechanism of these changes in the course of diabetes is not fully known. To determine whether there are myocardial ultrastructure differences between patients with diabetic cardiomyopathy (normal coronary angiograms) and diabetic patients with coronary artery disease, electron microscopy examination were performed of 70 sections received from seven biopsied patients (1F, 6M), average age 53 years (range: 42-60) with diabetes type II WHO (group A) without clinical evidence of prior coronary artery disease and hypertension, and 100 sections from 10 patients (2F, 8M), average age 54 years (range: 42-65) with diabetes and coronary atherosclerosis. These patients had clinical evidence of heart failure and were submitted to bypass-graft operations (group B). Endomyocardial biopsy tissues were obtained from the right ventricle without complications either during or after the procedure. Obtained biopsy specimens were fixed in 3% glutaraldehyde stabilized with 1M cacodylate buffer at pH 7.4, postfixed in 1% OsO4 on cacodylate buffer. The materials were then dehydrated and embedded in epon. The Irvin-Fischer test for statistical analysis was used. A p value < 0.05 was considered significant. The presence of focal mild loss of myofibrils (+) was statistically more frequent in the patients in A group (p < 0.05). It was found in 86% (6/7) of cases in A group, while in the B group was observed in 20% of (2/10) cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cardiomyopathy in diabetes. Ultrastructural examinations]. 828 30

Diabetic cardiomyopathy apparently has an important role in the increased cardiovascular morbi-mortality of diabetic patients and its cause is likely to be secondary to small vessel disease. We undertook the present study to compare small and large vessel disease in hearts of patients who died with coronary disease, and determine how diabetes and/or hypertension correlates with these findings. The paraffin blocks of 52 hearts were used in this study. Cases were selected if they died from coronary artery disease and excluded if they had a previous angioplasty, revascularization surgery, congenital, rheumatic or other causes of heart disease. They were divided in two groups; diabetics and non-diabetics and each group was subdivided in hypertensives an non hypertensives. They were matched by age and sex. DM duration was 11 +/- 6 years and known hypertension of 10 +/- 4 years with no significant differences between both groups. The results were recorded without knowledge of patients clinical findings. Atherosclerotic heart disease was more advanced in DM patients, with an increased prevalence of three vessels disease, and more extensive myocardial infarctions. Diabetic subjects had increased (non significant) basal membrane thickening of the capillaries. We could not find differences in parenchymal hypertrophy, interstitial edema, proliferative endothelial lesions and luminal width in middle and large size vessels. Hypertensive patients had increased perivascular fibrosis (NS). Our results suggest that advanced atherosclerotic heart disease is more common in diabetic patients and diabetic cardiomyopathy, if present, seems not to related to a particular structural microvascular disease.
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PMID:[The absence of characteristics lesions in the microcirculation of non-insulin-dependent diabetic patients]. 834 50

Diabetic cardiomyopathy, a condition characterized by the accumulation of carbohydrate-containing material surrounding the myocardial small blood vessels, has been studied in alloxan-diabetic normotensive and hypertensive rats. Immunochemical techniques were used to monitor several extracellular matrix constituents present in extracts of cardiac tissue, namely types I, IV and VI collagen, laminin and fibronectin, as well as myosin. These studies have indicated that after induction of diabetes, type VI collagen but none of the other matrix components studied, was significantly increased (from 2.29 +/- 0.04 mg/g in normal to 2.85 +/- 0.18 mg/g in diabetic ventricles, p < 0.01). Hypertension, whether induced by the clipping of one renal artery or genetically determined (spontaneously hypertensive rats), resulted in a similar elevation in type VI collagen (2.71 +/- 0.12 mg/g, p < 0.005 compared to normal rats). In the presence of diabetes plus hypertension the effect was not additive, the type VI collagen level being 2.93 +/- 0.15 (p < 0.001 compared to normal rats). Basement membrane collagen (type IV) in the myocardium appeared to be unaffected by diabetes or hypertension and the myosin contents of the hearts of the four experimental groups were similar. Quantitative determinations indicate that compared to type IV collagen, laminin or fibronectin, type VI collagen represents the major periodic acid-Schiff-reactive extracellular constituent of the rat ventricle. Its preferential increase in the heart in diabetes may provide insight into the molecular mechanisms of the diabetic microvascular disease.
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PMID:Increased rat myocardial type VI collagen in diabetes mellitus and hypertension. 845 34

To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy.
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PMID:Increased capillary permeability to albumin in diabetic rat myocardium. 847 28

Diabetes mellitus is often associated with a cardiomyopathy characterized by alterations in cardiac metabolism and declines in cardiac performance. We sought to determine whether exercise training would attenuate the depressed cardiac performance seen in diabetic animals. Female rats were divided into four groups: sedentary control, trained control, sedentary diabetics, and trained diabetics. After 1 week of training, we induced diabetes by intravenous injection of streptozotocin (65 mg/kg). We trained animals on a treadmill using a progressive protocol that plateaued at 27 m/min for 1 hr/day, 5 days/week for a total of 8 weeks. We measured cardiac output at a variety of left atrial filling pressures with an isolated working heart apparatus; glucose was the sole metabolic substrate for the heart. Training increased succinate dehydrogenase activity in the soleus muscle of exercised rats, but did not change heart and body weights or plasma glucose and thyroid hormone levels. The diabetic groups exhibited depressed cardiac outputs at high workloads compared to nondiabetics. Training increased the cardiac output of both sedentary and diabetic animals at high, but not low, preloads. We suggest that exercise can attenuate the severity of diabetic cardiomyopathy.
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PMID:Exercise training improves cardiac performance in diabetic rats. 850 62

Left ventricular function and morphology were assessed using M-mode echocardiography in 3 patients with diabetes mellitus associated with mitochondrial tRNA(Leu)(UUR) gene mutation, who were free of clinical, electrocardiographic, or thallium scan evidence of ischemic heart disease. Echocardiograms revealed hypertrophic cardiomyopathy in all 3 patients. Hypertrophy of the interventricular septum was mild in Cases 1 and 3 (12 and 13 mm, respectively) and severe in Case 2 (22 mm) (normal 7-10 mm). When they had neither signs nor symptoms suggestive of congestive heart failure, percentage fractional shortening (%FS), an index of wall motion of the left ventricle (normal > 28%), was normal in Cases 2 and 3 (28 and 32%, respectively) whereas it was slightly decreased in Case 1 (22%). In Case 1 with mild hypertrophy, the development of congestive heart failure was associated with a marked decrease in %FS to 13%; this patient responded well to diuretics and captopril and %FS rose to 22%. However, a mild decrease in %FS to 21% caused congestive heart failure in Case 2 with severe hypertrophy. His response to treatment was marginal. The present study indicates that mitochondrial DNA analysis should be done in patients with diabetic cardiomyopathy, and that sequential echocardiography is invaluable for the detection of hypertrophic cardiomyopathy and the management of subsequent myocardial dysfunction in patients with mitochondrial diabetes mellitus and cardiomyopathy.
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PMID:Hypertrophic cardiomyopathy in patients with diabetes mellitus associated with mitochondrial tRNA(Leu)(UUR) gene mutation. 856 88

We examined whether beraprost sodium (beraprost), a stable prostacyclin analogue, prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a bolus injection of streptozotocin in rat-tail vein. Four weeks after the induction of diabetes, the animals were treated with beraprost (30 micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK) activity. Nontreated diabetic rats have lower mean blood pressure, heart rate, left ventricular systolic pressure, and peak positive dP/dt at basal levels compared to age-matched normal rats. All of these changes were not improved in beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R ratio in the ECG were significantly increased in diabetic rats. These parameters were significantly improved by beraprost compared with nontreated diabetic rats. Additionally, beraprost significantly suppressed the elevation of plasma CK activity as compared with that in non-treated diabetic rats. Changes in peak positive dP/dt in response to isoproterenol were attenuated in nontreated diabetic rats as compared with age-matched normal rats and beraprost-treated diabetic rats. These results suggest that beraprost is capable of preventing diabetic cardiomyopathy without affecting hyperglycemic condition.
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PMID:Beneficial effects of beraprost sodium, a stable prostacyclin analogue, in diabetic cardiomyopathy. 856 22


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