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

Erythrocyte cation transport and intracellular calcium in 15 black type II diabetic hypertensives were compared with 11 otherwise similar non-diabetic hypertensives and 16 normal black adults. The diabetic hypertensives were then randomized into either a placebo group or a calcium-supplemented (600 mg/day) group and studied again after 4 weeks. Na+,K+-ATPase activity was significantly lower in both groups of hypertensives than in the normotensives. In contrast, Ca-ATPase activity was similar among the non-diabetic hypertensive and normotensives but was markedly (approximately 60%) suppressed in the diabetics, while intracellular calcium was proportionally elevated. Calcium supplements significantly increased Ca-ATPase activity and reduced intracellular calcium and blood pressure compared with the placebo group. We conclude that type II diabetes is characterized by a defect in Ca-ATPase which may be responsible for increases in intracellular calcium and vascular resistance and which is partially corrected by dietary calcium supplementation.
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PMID:Altered cation transport in non-insulin-dependent diabetic hypertension: effects of dietary calcium. 285 31

The epidemiology and etiology, pathophysiology, diagnosis, and treatment of congestive heart failure (CHF) are reviewed. CHF affects as many as 4 million Americans and is one of the most prevalent causes of death in hospitalized patients. Major risk factors for developing CHF include advanced age, male sex, hypertension, coronary artery disease, smoking, hypercholesterolemia, diabetes mellitus, and rheumatic heart disease. Heart failure results from decreased intrinsic myocardial contractility caused by one or more of three changes: (1) altered adrenergic nervous system function, (2) impaired delivery of calcium to contractile elements in the heart, and (3) reduced myosin-ATPase activity in the myocardium. The disease is progressive, and no intervention has yet been found to stop it effectively. CHF is diagnosed based on subjective signs and symptoms and objective assessment using auscultation, ECG, chest roentgenogram, laboratory tests, and noninvasive and invasive tests. Treatment of CHF begins with restriction of physical activity and sodium intake. Pharmacologic interventions start with either digitalis glycosides or thiazide diuretics; both may be used concomitantly as the disease progresses. Current studies are focusing on the use of angiotensin-converting enzyme inhibitors as first-line agents for CHF. When CHF worsens, loop diuretics are substituted for or added to the thiazide diuretics, and vasodilators are added to reduce the workload on the heart. Other inotropic agents, including the new bipyridine derivatives, may also be used. In patients not responding to these and other aggressive therapeutic interventions, cardiac transplantation is the only option. Despite advances in management of CHF, little improvement in overall survival has been demonstrated, and no intervention has stopped or reversed the progression of CHF.
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PMID:Current concepts in clinical therapeutics: congestive heart failure. 287 92

1. The effect of diabetes on renal sodium retention was investigated. 2. The technique involved retrograde perfusion from the renal veins via the kidneys, and then through the renal arteries and dorsal aorta. 3. Sodium retention by diabetic rat kidney was 58% lower than that in the normal rats. 4. Ouabain (15 mM) in perfusate increased sodium retention by 30% in normal rat kidney as compared to a 54% increase in diabetic rat kidney. 5. Ethacrynic acid (1 mM) in perfusate resulted in a 42% reduction in sodium retention in the normal rat kidney as compared to a 43% decrease in the diabetic rat kidney. 6. Control of hyperglycemia in diabetic rats with insulin therapy resulted in sodium retention that is not significantly different from that of normal rats. 7. The results suggest that diabetes has no effect on the peritubular ouabain-sensitive Na--K-ATPase pump, or the luminal ethacrynic acid-sensitive Na-K counter transport pump. Furthermore, the data suggest a reversible effect of diabetes on sodium retention during insulin therapy.
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PMID:Effect of diabetes on natriuresis in the presence of ouabain and ethacrynic acid in perfused rat kidney. 288 71

Alterations in ouabain inhibitable Na-K ATPase activity, polyol pathway activity, and myoinositol metabolism are part of a unifying hypothesis proposed to explain the pathogenesis of the chronic complications of diabetes mellitus. Direct measurements of renal ouabain inhibitable Na-K ATPase activity in animals with streptozotocin-induced diabetes show increased or decreased activity, depending on the nephron segment examined and the duration of diabetes. While myoinositol feeding corrects depressed Na-K ATPase activity in peripheral nerve of streptozotocin diabetic rats, the effect of myoinositol feeding on altered renal Na-K ATPase activity is unknown. To assess the effect of experimental diabetes on renal ouabain inhibitable Na-K ATPase activity and test the involvement of the polyol/inositol pathway, we assayed kidneys from normal, streptozotocin diabetic, and myoinositol-supplemented diabetic rats for renal ouabain-inhibitable Na-K ATPase, alkaline phosphatase, and tau-glutamyltranspeptidase (tau-GT) activity. Ouabain inhibitable Na-K ATPase activity, expressed per milligram of protein, is increased in the inner medulla of the diabetic kidney compared with normal and, expressed per microgram DNA, is increased in both the inner medulla and cortex. Myoinositol supplementation did not affect the increase in renal enzyme activity seen with streptozotocin diabetes. These observations suggest that the regulation of renal ouabain inhibitable Na-K ATPase activity, in streptozotocin diabetes, does not depend on supplemental myoinositol. These findings do not exclude the possibility that changes in polyol or myoinositol concentrations in a specific nephron segment may have pathogenetic significance for diabetic nephropathy.
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PMID:Renal ouabain inhibitable Na-K ATPase activity and myoinositol supplementation in experimental diabetes mellitus. 289 13

Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming.
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PMID:Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes. 293 7

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

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

The direct effect of insulin on the high-affinity Ca2+-Mg2+-ATPase was studied in kidney proximal tubular basolateral membranes (BLM) obtained from control and streptozocin-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. Plasma glucose of the diabetic animals was only mildly elevated (217 +/- 9 vs. 138 +/- 3 mg/dl). Both high- and low-affinity calcium-dependent Ca2+-Mg2+-ATPase activities were identified in the BLM. Enzyme activity in BLM from diabetic rats was higher at all Ca2+ concentrations tested due to a higher maximum velocity of the enzyme from NIDDM rats. The high-affinity Ca2+-Mg2+-ATPase activity was inhibited by trifluoroperazine (TFP) in both membranes. No difference in calmodulin content was found in the membranes from the diabetic and control rats. Insulin (16-200 microU/ml) significantly increased the high-affinity Ca2+-Mg2+-ATPase activity (17-40%) in membranes from control animals but had no effect on the enzyme activity in the membranes from the NIDDM rats. The basal activity of the enzyme at 0.1 microM free Ca2+ was higher in the BLM from the NIDDM animals compared to controls (17.8 +/- 0.5 vs. 14.7 +/- 0.8 nM Pi X mg-1 X min-1; P less than .02). There was no effect of insulin on the Ca2+-independent ATPase activity of BLM preparations. These findings demonstrate a defect in the ability of insulin to regulate the high-affinity Ca2+-Mg2+-ATPase activity in BLM from diabetic rats. Such a defect in enzyme activity may play a role in the mechanism of impaired insulin action observed in these NIDDM rats.
Diabetes 1986 Aug
PMID:Ca2+-Mg2+-ATPase activity in kidney basolateral membrane in non-insulin-dependent diabetic rats. Effect of insulin. 294 33

The present study provides histochemical evidence supporting the operation of the 'glucose-fatty acid cycle' in skeletal muscles taken 5 days after the administration of a single injection of streptozotocin. It also indicates that the cycle is more important in fast-oxidative-glycolytic (FOG) and slow-oxidative (SO) fibres than in fast-glycolytic (FG) fibres. Data from muscles taken 14 and 28 days after treatment suggest that lipid catabolism becomes progressively less important with time, and that muscles from longer-term diabetic rats rely on the aerobic and anaerobic breakdown of glucose by FOG and FG fibres to meet their cellular energy requirements. Although SO fibres appeared initially to be the least affected by streptozotocin-induced diabetes, the decline in their metabolic capabilities ultimately seemed to be greater than that in FOG fibres. Transformations in the biochemical characteristics of FOG and SO fibres occurred 14-28 days after streptozotocin treatment, in the absence of changes in actomyosin-ATPase activity. This supports the view that the division of skeletal muscle fibres into three or four distinct types on the basis of myosin- or actomyosin-ATPase activity is an oversimplification of the true situation.
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PMID:Histochemical evidence of changes in fuel metabolism induced in red, white and intermediate muscle fibres of streptozotocin-treated rats. 294 22

In rats, chronic diabetes is associated with depressed cardiac myosin ATPase activity and a shift from the predominant V1 isoenzyme to V3, correlating with depressed contractility. Rabbit myocardium consists mostly of the V3 isoenzyme, and therefore a switch to even more V3 isoenzyme in diabetes might not be possible and therefore not explain the mechanical abnormalities observed. To explore this, rabbits were made diabetic with 140-150 mg/kg of alloxan, and their hearts were studied 3 days, 1 mo, 3 mo, and 6 mo later. Ca2+-myosin-ATPase activity was decreased in the diabetic rabbit at 1, 3, and 6 mo, correlating with increased percent V3. Actin-activated Mg2+-ATPase activity was not significantly decreased in diabetics, but myofibrillar ATPase activity was decreased in 6-mo diabetic animals. When 3- to 4-mo diabetic animals were administered insulin for 3-4 additional months, myosin-ATPase activity and isoenzyme distribution normalized. These results correlate well with mechanical changes in papillary muscle from these same hearts. They suggest that in rabbit, as in rat, changes in cardiac contractile function are at least partially mediated by changes in myosin isoenzyme composition and are reversible with insulin.
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PMID:Effects of diabetes on cardiac contractile proteins in rabbits and reversal with insulin. 294 66


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