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)

We have previously described an antibody which will agglutinate red blood cells which had been incubated in vitro in D-glucose. This antibody is specific for the ring form of glucose, beta-D-glucopyranose. The current report demonstrates that without prior in vitro incubation with glucose, red blood cells from 36 of 38 patients with diabetes mellitus, and 7 of 70 patients not diagnosed as diabetic were agglutinated by this antibody. Strength of agglutination of red blood cells from diabetic patients correlated with both glucose (r = 0.61; p less than 0.001) and hemoglobin A1c levels (r = 0.50; p less than 0.01) in simultaneously obtained samples. This reactivity could be reversed by incubating red blood cells from diabetics for several hours in saline. This report suggests that red blood cells from diabetic patients have membrane-bound glucose that can be detected immunologically. Reversibility of the reaction and rapidity of in vitro glycosylation suggests short-term binding of glucose. To our knowledge, this is the first report documenting immunological detection of in vivo short-term reversible binding of glucose to cellular membranes.
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PMID:Agglutination of red blood cells from patients with diabetes mellitus by a polyclonal human antibody specific for D-glucose. 233 33

There is a growing evidence for that in modern societies the function of the cellular sodium-potassium pump (membrane-bound Na+ K+ ATPase) in several tissues in man cannot respond adequately to demands. This is not seen in any other free-living vertebrates on this earth. The clearly unphysiological very high intake of sodium-chloride (salt) and also alcohol is definitely playing an important role in the development of the common degenerating metabolic aberrations, e.g. essential hypertension, diabetes II and severe over-weight, in man. The special and overall important role of the sodium-potassium pump for optimal cellular function and regeneration with special reference to the vascular tissues is presented and discussed.
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PMID:The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. 258 82

Purkerson et al. have hypothesized that platelet aggregation and release reactions contribute to the progressive sclerosis of remnant nephrons. The suggested mechanism for platelet activation is disruption of endothelium by the high hydraulic pressures characteristic of remnant nephrons, with platelet exposure to basement membrane collagen. We herein postulate additional mechanisms whereby platelets might be activated in the microcirculation of remnant nephrons: (i) kinetic activation due to high plasma flow rates; (ii) close cell contact due to concentration of blood cells and platelets in the glomerulus; (iii) concentration of protein macromolecules that act as agonists for platelet release; (iv) glomerular release of saturated and monenoic fatty acids that stimulate platelet synthesis of thromboxane A2; (v) glomerular release of membrane-bound pro-coagulant factor, triggering a chain reaction that activates both platelets and the intraglomerular coagulation cascade. Platelet activation could play a pathogenetic role in many of the known derangements of structure and function in remnant nephrons. This paradigm may also be partially applicable to the glomerulosclerosis of diabetes mellitus.
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PMID:The role of platelets in progressive glomerulosclerosis: mechanisms for intraglomerular platelet activation and pathogenetic consequences. 264 24

The specific activities of membrane-bound maltase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20) in isolated brush border membranes (BBMs) of alloxan-induced diabetic, glucose-infused and maltose-infused rabbits were 30%, 140% and 160%, respectively, of those of control rabbits. Differences in the relative activities of trehalase (EC 3.2.1.28), another disaccharidase, in these groups were similar but less marked. However, the activities of two other marker enzymes of the brush border, alkaline-phosphatase and gamma-glutamyl transpeptidase, were similar in the 4 groups of rabbits. The decreases in the activities of the two disaccharidases were due to changes in the Vmax values of the enzymes without change in their Km values for maltose and trehalose. The maltase activities in the 4 groups showed similar dependences on Tris-HCl, KCl and NaCl. The electrophoretic profiles of the BBMs of the 4 groups on SDS-polyacrylamide gel showed slight differences. From these results, we conclude that diabetes, glucose infusion and maltose infusion probably change the concentrations of active enzymes in the BBM of the kidney in rabbits.
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PMID:Comparisons of maltase activities in kidney brush border membranes from normal, diabetic, glucose-infused and maltose-infused rabbits. 266 45

A diabetogenic strain of coxsackievirus B4 of human origin has been purified to study its biochemistry and diabetogenicity. Tissue culture cells infected with the virus contain two distinct types of particles--virions and membrane-bound virions (MBV). MBVs are lighter (p = 1.29) than virions (p = 1.34), and they contain relatively more protein than RNA. Virons contain four capsid proteins, VPI-4, of various molecular weights: VP1, 37,500; VP2, 36,000; VP3, 26,000; and VP4, 5,500. MBVs contain three of these proteins and several additional proteins of molecular weights 45,000 to greater than 92,500, possibly of host or viral origin. The RNA in each type of particle is a 35S molecule; T1 oligonucleotide fingerprint profiles suggest minor differences in the two RNAs. Hybridization experiments show a great deal of sequence homology between the RNA of the diabetogenic strain and the RNA of prototype CB4, which does not induce overt diabetes. MBVs are 10-70 times less infective than virions, yet they are more pathogenic in mice and induce significantly higher glucose intolerance (hyperglycemia). The hyperglycemic response appears to be lower in mice infected with both types of particles than in mice infected with MBVs alone. Thus, the two subpopulations of virions present in the diabetogenic strain differ biochemically and in their ability to induce diabetes.
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PMID:Purification and characterization of a strain of coxsackievirus B4 of human origin that induces diabetes in mice. 284 70

The responsiveness of parathyroid cells in insulin deficient and short-term diabetic rats was investigated by morphometric analysis. Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin. Parathyroid glands were stimulated for parathyroid hormone secretion by decreasing the serum calcium concentration through intravenous infusion of EGTA. Parathyroid cells of controls, insulin deficient, and short-term diabetic rats responded to reduced serum calcium by a 45% increase of the cell surface area. This increase is assumed to be the result of the membrane-bound transport of parathyroid hormone from the Golgi complex and secretory granules to the plasma membrane and subsequent exocytic release of parathyroid hormone induced by the low serum calcium concentration. Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone. It is also considered likely that synthesis of parathyroid hormone is not suppressed in short-term diabetes but that fat metabolism is disturbed leading to accumulation of lipid vacuoles.
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PMID:Unimpaired membrane dynamics in parathyroid cells in insulin deficient rats. 289 31

In an attempt to determine the mechanism of insulin resistance in the presence of obesity, we examined effects of insulin on insulin-sensitive phosphodiesterase (PDE) in spontaneously diabetic KK mice. Isolated fat cells prepared from epididymal adipose tissue were incubated, with or without insulin, for 10 min. In the case of subcellular fractionation, only membrane-bound PDE was activated by insulin, as was noted in the case of rat fat cells. The specific activity was decreased in KK mice compared with control C57BL/6 mice. The dose-response curve, expressed as a percent of the maximal insulin effect, shifted to the right and the increase of ED50 indicated a decreased insulin sensitivity in the KK mice. The maximal insulin effect did not change, either when expressed as a percent of the basal enzyme activity or when expressed on a per cell basis. Specific binding of [125I]-insulin in fat cells increased in KK mice and curvilinear Scatchard plots showed an increase of the high-affinity sites. These data indicate that impairment of PDE activation in fat cells of KK mice relates to postreceptor defects and the uncoupling may result in a decreased sensitivity.
Diabetes 1985 Sep
PMID:Insulin resistance of fat cells from spontaneously diabetic KK mice. Analysis of insulin-sensitive phosphodiesterase. 299 83

The effect of insulin on total and ouabain-inhibited membrane-bound adenosine triphosphatase (ATPase) activity in renal glomeruli isolated from adult white rats was examined. In concentrations of 1-10 micrograms/ml, insulin significantly stimulated the ouabain-inhibited (Na+ + K+)-ATPase activity, without affecting total (composite) ATPase activity. These results, coupled with previous findings demonstrating that glomerular (Na+ + K+)-ATPase activity is reduced in acute streptozotocin diabetes, suggest that the renal glomerulus is a target tissue with respect to this biologic effect of insulin.
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PMID:Insulin stimulates renal glomerular sodium-potassium adenosine triphosphatase activity. 300 70

To explore a possible link between diabetic nephropathy and the enhanced activity of the polyol pathway known to occur in diabetes, we examined several pertinent metabolic parameters in glomeruli isolated from control and streptozotocin-diabetic rats and assessed whether changes observed in diabetic glomeruli could be prevented by the oral administration of the aldose reductase inhibitor sorbinil. We found that glomerular polyol content is significantly increased in diabetes, whereas glomerular myo-inositol content is significantly reduced. The sorbitol accumulation and myo-inositol depletion were both completely prevented by sorbinil, which was given throughout the duration of diabetes. Activity of the membrane-bound sodium/potassium adenosine triphosphatase (Na-K-ATPase) was decreased in diabetic samples; this change was also completely prevented by sorbinil. Erythrocyte deformability is another factor that has been implicated in the pathogenesis of microangiopathic complications. The ability of red blood cells to undergo an adaptation in shape that permits passage through the smallest vessels is impaired in diabetes. Using blood from control, diabetic, and sorbinil-treated diabetic rats, we found that erythrocyte deformability was decreased in diabetic samples and that sorbinil treatment significantly improved this parameter. Thus, if the glomerular consequences of sorbitol accumulation, myo-inositol depletion, reduced Na-K-ATPase activity, and decreased erythrocyte deformability are pathogenetically implicated in diabetic nephropathy, the ability of sorbinil to impact on these changes suggests that it could favorably impact on the nephropathic process.
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PMID:Aldose reductase, glomerular metabolism, and diabetic nephropathy. 300 26

Insulin acutely inhibits the catecholamine-stimulated rise in cAMP levels in fat, liver, and muscle primarily through stimulation of the enzyme cAMP phosphodiesterase (PDE). Adipocytes from rat epidydimal fat pads were exposed to insulin and fractionated by centrifugation. Whereas the cytosolic fraction contained a low-affinity cAMP PDE that was unaffected by insulin, the activity of a high-affinity enzyme residing in a particulate fraction was increased by insulin. This enzyme activity could be solubilized with nonionic detergent and chromatographed on ion exchange followed by chromatofocusing. The resulting enzyme preparation was subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Silver staining revealed a single band with a molecular weight of 60,000. This apparent molecular weight was verified by calculation of the hydrodynamic properties of the enzyme. Evaluation of its kinetic properties indicated that the enzyme activity residing in this solubilized 60,000-Mr protein exhibited lower affinity than the membrane-bound enzyme but was still specific for cAMP. Activation of this enzyme may be one of the primary mechanisms by which insulin counteracts the effects of adenylate cyclase-stimulating hormones.
Diabetes 1986 Jun
PMID:Purification of putative insulin-sensitive cAMP phosphodiesterase or its catalytic domain from rat adipocytes. 301 73


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