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)

Alterations in erythrocyte plasma membrane properties (enzymatic activities and membrane fluidity) have been observed in patients affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). In order to verify whether these alterations are present also in gestational diabetes mellitus (GDM) we studied the plasma membranes obtained from two different cellular types (erythrocyte from both mother and cord blood and placenta syncytiothrophoblast cell) of 16 healthy pregnant women and 15 women affected by GDM. The following determinations were performed on the membrane preparations: Na+/K(+)-ATPase activity, acetyl-cholinesterase (AchE) activity, membrane fluidity and cholesterol:phospholipid ratio. We observed a reduction of both enzymatic activities and a decrease of membrane fluidity in maternal and cord blood erythrocytes and in syncytiotrophoblast plasma membranes in GDM pregnant women in comparison with controls. The cholesterol to phospholipid ratio was significantly lower in the erythrocyte membranes of women affected by GDM than in normal pregnant women, while it was increased in the cord blood erythrocyte membranes and in placental membranes in GDM in comparison with controls. The present study found, in GDM patients, a membrane alteration similar to the abnormality reported in IDDM and NIDDM (i.e. decreased Na+/K(+)-ATPase activity), while opposite modifications were observed with regard to other membrane activities and properties. The different membrane alterations observed in GDM with respect to IDDM and NIDDM might be linked to the different degree of metabolic control, on the contrary the reduced Na+/K(+)-ATPase activity might be a primary event in the pathogenesis of diabetes mellitus per se and might constitute a signal of high risk of developing the disease later in the women affected by GDM during pregnancy.
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PMID:Modifications induced by gestational diabetes mellitus on cellular membrane properties. 165 18

Aldose reductase (EC 1.1.1.21) is implicated in the pathophysiology of diabetic complications. In this paper we determined the activities of aldose reductase and ATPases of the erythrocytes in 17 patients with Type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). In the aldose reductase assay we used fluorometric method to avoid the disturbance of hemoglobin. With dihydronicotinamide adenine dinucleotide (NADH), we verified it was aldose reductase but not aldehyde reductase II that was activated in the erythrocytes of the patients with NIDDM. The aldose reductase activity of the erythrocytes in the patients was significantly higher (P less than 0.01) than that in the controls. The activity of Na+/K(+)-ATPase of the patients was significantly lower (P less than 0.01) than that of the controls. The activities of Ca(2+)-ATPase and Mg(2+)-ATPase on the erythrocyte membranes of the patients were similar to those of the controls. At the same time we measured the seven nucleotide concentrations in the erythrocytes of the patients. In this experiment we used ultrafiltration method, instead of acid precipitation to make it possible to determine dihydronicotinamide adenine dinucleotide phosphate (NADPH) and NADH. The concentrations of ATP, ADP and AMP were similar to those of the controls. The concentrations of NADPH, NAD+ and NADH in the erythrocytes of the patients were significantly lower (P less than 0.01, 0.05 and 0.05 respectively) than those of controls. The concentration of nicotinamide adenine dinucleotide phosphate (NADP+) in the patients was significantly higher (P less than 0.01) than that of controls.
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PMID:Activities of aldose reductase, ATPases, and nucleotide concentrations of erythrocytes in patients with type 2 (non-insulin-dependent) diabetes mellitus. 166 Dec 22

Na(+)-K(+)-ATPase provides the driving force for cellular Na+ transport and exists in multiple isoforms that differ in ouabain sensitivities. We report that the Ki for ouabain inhibition of glucose-evoked short-circuit current, determined in intact rat ileal mucosa mounted in Ussing chambers, is higher in streptozocin-induced chronically diabetic rats than in age-matched controls. The changes in ouabain sensitivity seen in diabetes also occurred when intact ileum of age-matched controls was incubated in vitro with 2.8 x 10(-5) M glucagon for at least 80 min. The effect of glucagon was blocked by cycloheximide, indicating a role for protein synthesis. This suggests that changes in ouabain sensitivity seen in diabetes are produced by glucagon, the serum concentration of which increases in diabetes. Ouabain-dependent phosphorylation of Na(+)-K(+)-ATPase (backdoor phosphorylation) revealed a higher Km for phosphate in intestinal basolateral membranes obtained from diabetic rats compared with age-matched controls, again confirming a decrease in ouabain sensitivity. Furthermore, the mRNA encoding the alpha 1-isoform was upregulated 2.6-fold in chronically diabetic intestines. This suggests that the ouabain sensitivity seen during diabetes may be due to upregulation of the alpha 1-isoform, known to be less sensitive to ouabain than the other isoforms.
Diabetes 1991 Dec
PMID:Diabetes mellitus and glucagon alter ouabain-sensitive Na(+)-K(+)-ATPase in rat small intestine. 166 91

The effects of alpha-receptor blockade on nerve conduction, hypoxic resistance, ouabain-sensitive Na(+)-K(+)-ATPase, nerve polyols, and capillary density were examined in streptozocin-induced diabetic (STZ-D) rats. Nondiabetic and untreated diabetic control groups were used. Diabetes duration was 2 mo. There were two treated diabetic groups. A "prevention" group received 5 mg/kg prazosin for 2 mo from the induction of diabetes. A "reversal" group was untreated for the 1st mo and was given prazosin for the subsequent month. Conduction was measured in motor nerves supplying tibialis anterior and gastrocnemius muscles and sensory saphenous nerve. Diabetes resulted in 15-29% reductions in conduction velocity (P less than 0.01). In the prevention group, conduction deficits were minimal compared with untreated diabetes (P less than 0.01). In the reversal group, motor conduction was also substantially improved, although sensory conduction was not significantly affected. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (P less than 0.01). This was largely prevented by prazosin treatment (P less than 0.01), although treatment had a lesser effect in the reversal group. Treatment had no effect on nerve polyol levels or Na(+)-K(+)-ATPase activity. Functional improvements with prazosin were probably based on increased vasa nervorum perfusion. There was a 20% elevation of endoneurial capillary density (P less than 0.01) in both prevention and reversal groups. We conclude that vascular factors play an important role in the etiology of experimental diabetic neuropathy, and functional changes may be corrected by chronic vasodilator treatment.
Diabetes 1991 Dec
PMID:Effects of chronic alpha-adrenergic receptor blockade on peripheral nerve conduction, hypoxic resistance, polyols, Na(+)-K(+)-ATPase activity, and vascular supply in STZ-D rats. 166 93

Na+/K(+)-ATPase was evaluated in the retina and kidney of the spontaneously diabetic BB/Wor rat after 1 and 4 months of insulin dependency. Retinal synthesis of the Na+/K(+)-ATPase was measured during a 2-h intravitreal pulse of [35S]methionine and analyzed by SDS-PAGE and scintillation counting. Synthesis of the alpha-1 and 'alpha(+)' (includes both alpha-2 and alpha-3) isoforms of the catalytic subunit was increased 123% and 69%, respectively at 4 months. Increases were also suggested at 1 month, but were not significant. The diabetes-dependent peak of synthesis in long-term diabetic rats turned over rapidly and by 3 days after intravitreal labeling, radioactively labeled enzyme was equal in both control and diabetic retinae. The amount of axonally transported, labeled enzyme recovered from endings of the optic nerve in the superior colliculus paralleled retinal labeling. Significant renal hypertrophy (48%) was noted at 4 months, but not at 1 month. The strophanthidin-inhibition constant for diabetes-induced renal enzyme was the same as for control enzyme (approx. 10(-4) M), indicating that diabetic renal hypertrophy does not induce a Na pump isozyme that is more sensitive to cardiotonic steroids. SDS-PAGE of the renal enzyme also failed to indicate more than one isoform of the alpha subunit.
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PMID:Molecular isoforms of Na+/K(+)-ATPase in the nervous system and kidney of the spontaneously diabetic BB/Wor rat. 166 41

Digitalis-like substance (DLS) was measured by Na-K-ATPase inhibitor (ATPI) activity and digitalis-like immunoreactivity (DLI) in 100 patients with type II diabetes. Hypertensive diabetic patients with a positive family history for hypertension had high ATPI levels compared with those patients with a negative family history for the disease. DLI level did not differ between groups. There was no significant difference in ATPI and DLI levels among three groups based on level of urinary albumin excretion. These data suggest that a circulating factor (or circulating factors) determined by ATPI may be linked with genetic factors in the development of hypertension, but not to the development of diabetic nephropathy.
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PMID:Elevated endogenous Na-K-ATPase inhibitor activity in hypertensive diabetic patients with a family history of hypertension. 166 15

Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na(+)-Ca2+ exchanger activity. This defect limits the ability of of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
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PMID:Cardiomyopathy associated with noninsulin-dependent diabetes. 166 89

Na-K ATPase activity in the brain decreased significantly after diabetes was induced with streptozotocin in rats. Largest decreases were observed in the hippocampus (-30%) and the cerebral cortex (-26%). Smaller decreases were observed in the thalamus (-13%), hypothalamus (-11%) and brain stem (-10%). Na-K ATPase activity in the striatum and the cerebellum were not significantly decreased. The varied decreases suggest that the regional variation of the enzyme is enhanced in the diabetic state. The enzymes of glucose metabolic pathway, namely hexokinase, lactate dehydrogenase and citrate synthase in the brain regions largely remained unchanged although increases in lactate dehydrogenase were observed in some regions. Acetylcholinesterase activity, a marker for the cholinergic system, remains unaltered in the brain during diabetes. The results are discussed with respect to the possible metabolic factors which alter the Na-K ATPase in the brain and its comparison with the peripheral nerve.
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PMID:Diabetes induced by streptozotocin causes reduced Na-K ATPase in the brain. 166 46

Diabetes mellitus caused significant reduction in serum testosterone and accessory sex glands weight. The sperm content of epididymal regions also decreased. Among the epididymal regions, the cauda epididymidal tissue alone showed significant reduction in Na(+)-K+ ATPase activity. However, Mg2+ ATPase activity was lowered in caput epididymidis only. Specific activity of Ca2+ ATPase significantly decreased in caput and cauda epididymides. All three ATPases decreased significantly in caput epididymidal spermatozoa leaving cauda epididymidal spermatozoa unaffected. Specific activity of alkaline phosphatase was suppressed in caput epididymidis and in the spermatozoa collected from caput and cauda epididymides, while the acid phosphatase was unaffected. In general, the results are suggestive of definite influence of diabetes on epididymal phosphatases which is region specific. Diabetes induced decrease in phosphatases may have an impact on secretory and absorptive functions of epididymis and thus on sperm maturation.
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PMID:Effect of diabetes mellitus on epididymal enzymes of adult rats. 166 46

The effects of streptozotocin induced diabetes on rats were studied. The animals showed an increase in blood glucose concentration and a loss of weight from both the body and the heart. Loss of weight from the heart was less severe leading to an increased heart to body weight ratio. Study of element concentrations by X-ray microanalysis showed that there was an increase in intracellular Na concentration in cardiac myocytes from the diabetic animals, but no change in Mg. These results agree with studies which show changes in Na/K ATPase after the onset of diabetes.
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PMID:Changes in sodium concentration in cardiac myocytes from diabetic rats. 182 9


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