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)

Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree.
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PMID:Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features. 15 9

14 national groups have collaborated under WHO auspices to select, from local defined populations of individuals with clinical diabetes, groups of approximately 500 within the age range 35--55 yr stratified by age, sex, and known duration of diabetes. In each center, the selected patients were submitted to a standardized study protocol, which included systematic inquiry (WHO questionnaire) for the presence of symptoms of angina pectoris, history of myocardial infarction, presence of intermittent claudication, and cigarette smoking history. Examination included standard biometry, blood pressure measurement, 12-lead (centrally Minnesota coded) electrocardiography, and central laboratory measurement of serum cholesterol and creatine. Ophthalmoscopic and urinary examinations were also included. The prevalence of arterial disease symptoms and electrocardiographic abnormalities show very large variation between countries, the lowest rates generally being found in the Oriental samples and the highest in the European. "Risk factors" for arterial disease (blood pressure, serum cholesterol, and cigarette smoking) also vary widely between diabetic groups. Although data are not yet complete, these differences appear unlikely to explain the variation in the atherosclerotic morbidity observed. Diabetic women were at least as vulnerable to arterial disease as diabetic men. A high prevalence of nonspecific abnormalities of the repolarization phase of the ECG was found, even in groups where ischemic abnormalities were rare. The origin of these is uncertain; they may represent variable local changes or possibly diabetic cardiomyopathy. This preliminary report confirms and quantifies previous indications that the impact of atherosclerotic disease on persons with diabetes varies considerably between national groups, in broad terms, running parallel with the variations in prevalence in the populations in general and suggesting that cultural and/or ethnic factors are more important determinants of atherosclerosis in diabetic individuals than is the diabetic state per se.
Diabetes Care
PMID:The WHO multinational study of vascular disease in diabetes: 2. Macrovascular disease prevalence. 52 Jan 23

Left ventricular function was assessed by measuring sytolic time intervals in insulin-requiring diabetics with and without significant microangiopathy. The results were compared with those in normal controls. Significant microangiopathy was defined as proteinuria over 3 g/24 h or proliferative retinopathy. Left ventricular function was also assessed one and a half years later by echocardiography in four patients with microangiopathy. Patients with angina, previous myocardial infarction, hypertension, and alcoholism were excluded. All had normal electrocardiograms and chest radiographs. Diabetics with microangiopathy had impaired left ventricular function, whereas those with uncomplicated diabetes had normal function. This finding supports the existence of a specific diabetic cardiomyopathy due to microangiopathy rather than the metabolic defect. The association of microangiopathy and impaired left ventricular function may explain the high immediate mortality and the high incidence of cardiogenic shock and congestive heart failure after myocardial infarction in diabetics.
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PMID:Diabetic cardiomyopathy: the preclinical phase. 86 81

To investigate a mechanism of diabetic cardiomyopathy, we examined an alteration of cardiac alpha 1-adrenoceptor (alpha 1-AR) signaling in streptozotocin-induced diabetic rats. In diabetes, the cell surface alpha 1-AR concentration on isolated cardiac myocytes decreased by 45% without any change in the dissociation constant, and, moreover, norepinephrine (NE)-stimulated ventricular inositol 1,4,5-trisphosphate (IP3) production was also decreased by 34%. In contrast, basal ventricular protein kinase C (PKC) activity was elevated in both cytosolic (by 98%) and membrane (by 41%) fractions in diabetes. All of these abnormalities seen in diabetes were reversed by chronic insulin treatment. Rapid activation of PKC by phorbol ester in the normal rat heart revealed decreases in both receptor number (by 19%) and NE-stimulated IP3 production (by 21%). These results indicate that the impairment of cardiac alpha 1-AR signaling is closely associated with the diabetic state and may be linked, at least in part, with the abnormal activation of cardiac PKC.
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PMID:Abnormalities in cardiac alpha 1-adrenoceptor and its signal transduction in streptozocin-induced diabetic rats. 132 23

Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.
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PMID:Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats. 138 Oct 8

The objective of this study was to test the hypothesis that excessive severity of ischaemic heart disease in diabetics is due, in part, to capillary inadequacy. Sections from autopsied hearts of diabetic patients with and without myocardial infarction as well as from those of patients with infarcts and no diabetes were used for morphometric studies of intramural microvessels in areas without infarction. Normoglycaemic patients with normal hearts were also examined. Two to five transverse sections from each of 44 hearts (stained with methenamine silver) were examined for capillary numerical density, capillary to myofibre ratios, and myofibre diameters. Averages for each case and totals for each group were calculated and compared. Normoglycaemic patients with infarcts had increased morphometric values. Diabetics with infarcts had significantly lower capillary densities than the other groups. In conclusion, it is suggested that in diabetes there is an inadequate ischaemia-induced, reactive angiogenesis. This may contribute towards increased myocardial vulnerability in further ischaemic injury and perhaps to diabetic cardiomyopathy.
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PMID:Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material. 151 82

Early manifestations of non-atherosclerotic cardiomyopathy, a recognized complication of diabetes in adults, have been suggested to contribute to depressed levels of aerobic fitness described in children and adolescents with this disease. This study measured components of aerobic fitness and cardiovascular function during maximal cycle ergometer exercise in 11 insulin-dependent diabetic boys aged 10.2-16.5 years. Mean duration of diabetes was 4.5 years. Eleven non-diabetic subjects matched for age, body size, and regular physical activity served as controls. No differences in maximal oxygen uptake or heart rate were observed between the two groups, nor were any significant differences recorded in submaximal stroke volume, cardiac output, heart rate, and pressure-rate product. This study failed to reveal any evidence of functional myocardial disease in children and young adolescents with diabetes, suggesting that manifestations of diabetic cardiomyopathy should not be expected during the pediatric years. Moreover, these findings indicating normal cardiovascular function in young diabetic subjects imply that regular levels of habitual physical activity are more likely to affect aerobic fitness in these patients rather than influences of the diabetic state itself.
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PMID:The influence of diabetes mellitus on cardiovascular function in children and adolescents. 152 62

Diabetes mellitus is associated with excessive cardiovascular morbidity and mortality. Patients with diabetes mellitus suffer premature and severe atherosclerosis, and the relative impact is greater in women than in men. Clinical, experimental and pathological studies support the existence of a specific cardiomyopathy associated with diabetes mellitus. The cardiomyopathy plays an essential role in the pathogenesis of primary myocardial involvement, resulting in ventricular dysfunction, diminished cardiac pump performance and eventually overt heart failure. The authors discuss coronary heart disease and diabetic cardiomyopathy and indicate relevant treatment regimens.
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PMID:[Myocardial disease in diabetes mellitus]. 155 23

The hypothesis that diabetes mellitus provokes a specific cardiomyopathy is supported by numerous clinical, epidemiological and anatomopathological studies. However, the frequent association of diabetes mellitus with other conditions, such as hypertension and coronary atherosclerosis, both capable of causing the dysfunction of the cardiac muscle, makes it difficult to interpret many of the data reported in the literature and contributes to the continuing debate regarding the effective existence of diabetic cardiomyopathy and its possible pathogenetic mechanisms. In clinical terms, diabetic cardiomyopathy is manifested both as an altered diastolic and/or systolic phase, assessed using various non-invasive techniques, or as congested cardiac decompensation. The pathogenesis of diabetic cardiomyopathy is still not altogether clear. The alteration of the smallest coronary vessels might be responsible for the increased interstitial fibrosis found in the heart of diabetic patients. In this paper numerous data from the literature on this argument are reported and the authors advance the hypothesis that endothelial dysfunction may play a pathogenetic role in the development of cardiopathy.
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PMID:[Diabetic cardiomyopathy: possible pathogenetic role of coronary microcirculation]. 163 Jun 65

Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF.
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PMID:Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane. 164 1


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