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

The BB or BB/Worcester (BB/W) rat is widely recognized as a model for human insulin-dependent diabetes mellitus (IDDM). Of at least three genes implicated in genetic susceptibility to IDDM in this strain, one is clearly linked to the major histocompatibility complex (MHC). In an attempt to define the diabetogenic gene(s) linked to the MHC of the BB rat, cDNA clones encoding the class II MHC gene products of the BB diabetes-prone and diabetes-resistant sublines have been isolated and sequenced. For comparison, the beta 1 domain of class II genes of the Lewis rat (RT1L) were sequenced. Analysis of the sequence data reveals that the first domain of RT1.D beta and RT1.B beta chain of the BB rat are different from other rat or mouse class II sequences. However, these sequences were identical in both the BB diabetes-prone and BB diabetes-resistant sublines. The significance of these findings is discussed in relation to MHC class II sequence data in IDDM patients and in the nonobese diabetic (NOD) mouse strain.
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PMID:Molecular characterization of MHC class II antigens (beta 1 domain) in the BB diabetes-prone and -resistant rat. 278 84

To assess the effects of chronic diabetes on in vivo myocardial reactivity to beta 1 adrenergic receptor stimulation and to evaluate the therapeutic effect of exercise training in preventing the cardiac abnormalities induced by diabetes four groups of rats were studied: sedentary control, trained control, sedentary diabetic, and trained diabetic. Trained rats were adapted to treadmill running before the induction of diabetes with streptozotocin 55 mg.kg-1 iv. The duration, speed, and grade of exercise were then progressively increased during eight weeks of training until the rats could run for 90 min at 18 m/min, 5% grade. A training effect was confirmed by an increase in plantaris muscle cytochrome oxidase activity. In vivo cardiac contractile performance was assessed by intracardiac catheterisation. Heart rate, left intraventricular peak systolic pressure, and positive and negative dP/dt were measured under basal conditions and after the intravenous administration of dobutamine 10(-10) to 5 x 10(-7) mol.kg-1 body weight. Under basal conditions, there were no differences among the four groups in left intraventricular peak systolic pressure, positive dP/dt, and heart rate, but negative dP/dt was lower in both diabetic groups. The response to dobutamine of the sedentary diabetic group, as reflected in the measured cardiodynamic variables, was significantly attenuated compared with that of the sedentary control group. Exercise training tended to improve cardiac function towards the level detected in the sedentary controls; however, the differences between sedentary and trained diabetic groups were not statistically significant. Exercise training also did not significantly alter the response of the control group to dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depressed in vivo myocardial reactivity to dobutamine in streptozotocin diabetic rats: influence of exercise training. 285 56

Almost all beta-adrenergic blockers, regardless of their pharmacologic characteristics, appear to have blood pressure-lowering activity in hypertensive patients. Comparisons between nonselective beta-blocking agents, such as propranolol and nadolol, with beta 1-selective drugs, such as metoprolol, atenolol and acebutolol, have demonstrated close similarities in their antihypertensive effects in patients. Similarly, beta blockers with and without intrinsic sympathomimetic activity (ISA) have comparable antihypertensive effects. However, beta-selective agents may offer some advantages over conventional beta blockers in hypertensive patients with concurrent conditions such as chronic obstructive airways disease, peripheral vascular disease, diabetes and hyperlipidemia. Beta 1-selective drugs are also preferred in diabetic patients receiving hypoglycemic agents because they do not interfere with glycogenolysis. Agents lacking ISA, such as propranolol, acutely increase peripheral resistance. beta blockers with ISA usually lower resistance. ISA may also minimize the bradycardia frequently found in elderly patients. Agents with ISA may protect against the decrease in high density lipoprotein cholesterol and the modest increase in triglycerides noted with some beta blockers that do not have ISA. Thus, in a large number of clinical situations in which hypertension is found, the properties of beta 1 selectivity and ISA allow beta blockers to be used with greater safety. Therefore, agents possessing both of these properties may be particularly valuable.
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PMID:Clinical significance of beta 1-selectivity and intrinsic sympathomimetic activity in a beta-adrenergic blocking drug. 288 76

Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double-blind randomised order at weekly intervals. Supine resting heart rate, physiological tremor and blood glucose were measured before, 2 and 4 h after dosing, and ambulatory heart rate monitored for 24 h. Supine resting heart rate was significantly lowered by atenolol both at 2 and 4 h, and increased on pindolol at 4 h. Heart rate was unaffected by epanolol compared with placebo. Heart rate during the 'waking' period (14.00-23.00 h) was lower than placebo after epanolol and atenolol but unaffected by pindolol. During the 'sleeping' period (23.00 h-08.00 h) heart rate was significantly increased by pindolol, lowered with atenolol and unaffected on epanolol. Pindolol significantly increased physiological tremor at 4 h. No differences were seen between epanolol, atenolol and placebo. Plasma glucose was significantly increased by pindolol 2 h after dosing. These results suggest that pindolol probably produces its partial agonist activity at both beta 1- and beta 2-adrenoceptors, while the partial agonist activity of epanolol is beta 1-selective. Despite abnormal cardiovascular reflex tests in these diabetics, the heart rate responses obtained in this study after beta-adrenoceptor blockade were surprisingly normal, and suggest that the concept of 'cardiac denervation' in diabetes requires modification.
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PMID:Effects of beta-adrenoceptor blockade on heart rate and physiological tremor in diabetics with autonomic neuropathy. A comparative study of epanolol, atenolol and pindolol. 288 87

Insulin-dependent diabetes (IDD) is positively associated with HLA-D proteins. A critical question is whether or not sequence differences within the HLA-D coding region are the same or different in diabetics and normal individuals of the same haplotype. We have isolated both DR beta 1 alleles from a Dw4/LD MN2 cDNA library and compared them to DR beta 1 genes isolated from normal individuals of the same Dw phenotype. We found no nucleotide differences in the coding region between the normal and diabetic alleles of DR beta 1 suggesting to us that DNA differences other than the DR beta 1 coding region may account for the observed association of HLA-D and diabetes.
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PMID:Comparison of DR beta 1 alleles from diabetic and normal individuals. 288 1

Diuretics and beta blockers are the mainstay in treating mild and moderate systemic hypertension, but there is controversy as to which should be used first. Recent evidence of an increase in sudden death and a greater number of intolerable side effects in the diuretic-treated groups in the Multiple Risk Factor Intervention Trial in the U.S. and the Medical Research Council Trial in Great Britain has prompted some to suggest beta blockers as first-line therapy. However, beta blockers also have side effects, such as decreased ventricular function in patients with mild heart failure, increased airways resistance in those with chronic obstructive lung disease, increased plasma lipids, in particular low density lipoprotein cholesterol, and increased problems in patients with peripheral vascular disease and those with diabetes requiring insulin treatment. Many new beta-blocking drugs with different pharmacokinetic and pharmacodynamic properties allow the physician to choose the best one for each patient. beta-blocking drugs with long durations of action, high levels of bioavailability, beta 1 selectivity and intrinsic sympathomimetic activity appear most suitable for therapy. Cardioselectivity is suggested for patients with obstructive lung disease and peripheral vascular disease, and diabetic patients who take insulin. Long durations of action permit infrequent administration and recently agents with intrinsic sympathomimetic activity have been shown to have less effects on plasma lipid levels. Acebutolol also reduces ventricular arrhythmias, and may therefore be used to reduce sudden death in patients with coronary artery disease. The pharmacokinetic and pharmacodynamic properties of beta-blocking drugs can indicate the most appropriate choice for hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetic and pharmacodynamic properties of beta-blocking drugs influencing choice in treatment of systemic hypertension. 288 49

The aim of the present study was to check whether equal, therapeutically relevant, positively inotropic doses of different adrenergic agents elicit equal inotropic and metabolic effects in 6 type I-diabetics as in 6 matched nondiabetic subjects. The effects of increasing doses of norepinephrine (NE)- and orciprenaline (0.12, 0.20, 0.33 microgram/kg min) on heart function (systolic time interval, heart rate, blood pressure) and on serum fatty acid (NEFA), glucose, lactate, pyruvate and insulin concentrations were recorded. In the therapeutic dose range, NE, and orciprenaline elicited in diabetics without clinical signs of any cardiovascular disease a diminished myocardial inotropic response (20-40%), less marked vascular effects (vasoconstriction, vasodilatation), but greater metabolic changes in right atrial blood (NEFA, pyruvate, lactate) compared to matched controls (p less than 0.05). The smaller increase of cardiac performance in diabetics to exogenous catecholamines cannot be explained by sympathetic cardiac denervation, since chronotropic beta 1-beta 2-stimulation with orciprenaline provoked nearly equal dose-dependent changes in diabetics and controls. It is suggested that the smaller positive inotropic effect during NE and orciprenaline infusion in type I-diabetics is a result first of all of alterations in myocardial energy turnover in diabetes due to reduced myocardial glucose utilization. It seems necessary to secure continuous myocardial glucose utilization and subnormal NEFA concentrations in the serum during the therapeutic application of inotropic adrenergic agents in severe cardiac failure and cardiogenic shock in diabetics.
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PMID:Interaction between glucose utilization and left ventricular heart function in type I-diabetics. 338 68

The effect of acute and chronic beta- and alpha-adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% VO2max) was investigated in control and insulin-dependent diabetic subjects. In protocol I, subjects were studied during exercise alone, exercise plus intravenous propranolol, and exercise plus intravenous phentolamine. In both the control and diabetic groups, exercise alone produced a modest increase in the plasma potassium concentration (0.31 +/- 0.06 meq/l), while propranolol exacerbated this hyperkalemic response. In contrast, the increment in plasma potassium during phentolamine was similar to exercise alone in normals but was 26% (P less than 0.05) lower in the diabetic group. In protocol II, the effect of chronic (5 days) beta-adrenergic blockade on potassium homeostasis was examined. Subjects participated in three studies: exercise alone, exercise plus propranolol (beta 1/beta 2-antagonist), and exercise plus metoprolol (beta 1 antagonist). In the nondiabetic group, both propranolol and metoprolol were associated with a 40% greater increase in potassium compared with exercise alone. In the diabetic group, propranolol, but not metoprolol, was associated with a deterioration in potassium tolerance. In no study could the alterations in potassium homeostasis be explained by a change in urinary potassium excretion. In summary, alpha-adrenergic blockade ameliorates exercise-induced hyperkalemia in diabetic but not in control subjects, nonspecific beta-adrenergic blockade causes a greater increment in potassium when compared with exercise alone, and specific beta 1-adrenergic blockade exacerbates exercise-induced hyperkalemia in control, but not in diabetic subjects. These results indicate that both alpha- and beta-adrenergic regulation of extrarenal potassium metabolism is altered in insulin-dependent diabetes mellitus.
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PMID:Adrenergic modulation of potassium metabolism during exercise in normal and diabetic humans. 354 63

The association of HLA-DR4 with rheumatoid arthritis strongly implicates genes of the major histocompatibility complex (MHC) as contributing to disease susceptibility. Molecular analysis of MHC genes expressed on haplotypes in association with HLA-DR4 reveals that at least six different alleles of the DR beta 1 locus and at least three different alleles of the DQ beta locus occur on different DR4+ haplotypes. Some of these allelic differences are quite substantial, and others are rather subtle, involving as few as two amino acids. The analysis of individual DR and DQ alleles in rheumatoid arthritis identifies some DR4+ genes strongly associated with disease susceptibility and some DR4+ genes which are not. The Dw4(DR4) and Dw14(DR4) DR beta 1 genes appear to represent specific alleles which confer disease risk in RA; other DR beta 1 genes, such as Dw10(DR4), may represent DR beta genes altered during evolution which have lost their contribution to RA susceptibility. DQ beta 3.1(DQw3) and DQ beta 3.2(DQw3) DQ beta genes, which are present on DR4+ haplotypes, represent discrete variable alleles not directly implicated in RA, but which account for HLA-DR4 associations with other diseases, such as the association of DQ beta 3.2(DQw3) with Type I diabetes.
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PMID:The molecular basis for HLA class II associations with rheumatoid arthritis. 355 32

Criteria for the diagnosis of exercise hypertension have not yet been established. Published values for blood pressure increase during dynamic exercise in normotensive healthy persons differ greatly dependent on age, sex, heart frequency and load of dynamic exercise. Upper normal systolic values during exercise reach levels between 200 and 230 mm Hg. The incidence of exercise hypertension is therefore reported to range from 1 to 10% of the total population. Follow-up studies show that 10 to 60% of persons with isolated exercise hypertension proceed to chronic arterial hypertension. No results are available on exercise hypertension as a risk factor in contrast to the well-known link between increased systolic and diastolic casual blood pressure and cardiovascular diseases. The development of left-ventricular hypertrophy depends mainly on the average systolic blood pressure during a 24-hour period. Peak values of systolic blood pressure during the day or blood pressure variability are less important. Drug treatment of isolated exercise hypertension is not generally accepted. Non-drug treatment is to be preferred, e.g. weight reduction in overweight, dietary sodium restriction and endurance training. Drug treatment must be considered, if non-drug treatment is unsuccessful and/or risk factors, for example hypercholesterolemia, diabetes, cigarette smoking, or complications of target organs, i.e. coronary heart disease or cerebral infarction, do exist. In antihypertensive treatment of increased exercise blood pressure, the influence of the drugs on the hemodynamic and metabolic parameters must be observed, especially in patients with concomitant coronary heart disease. Increases in blood pressure due to dynamic exercise are better attenuated by antihypertensive drugs than those caused by isometric exercise. The drugs of choice are beta-blockers, preferably beta 1-blockers without ISA. Alternatively, calcium antagonists of the verapamil-type or ACE-inhibitors may be used. In contrast to other antihypertensive drugs, labetalol, calcium antagonists and ACE-inhibitors have no influence on the exercise-induced increase of cardiac index and therefore little effect on the work capacity of the circulatory system.
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PMID:[Differential therapy of exercise hypertension]. 358 8


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