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)

Glucose can react with the lysine residues of low-density lipoproteins (LDLs) and convert the lipoprotein to a form with a receptor-mediated uptake by cultured cells that is impaired. However, in contrast to other modified lipoproteins taken up by both murine and human macrophages via the scavenger-receptor pathway that may induce the formation of foam cells, glycosylated LDL is not recognized by murine macrophages, and thus far, it has not been shown to lead to marked intracellular accumulation of cholesterol in human macrophages. This study illustrates that glycosylated LDL incubated with human monocyte-derived macrophages, at a concentration of 100 micrograms LDL/ml medium, stimulates significantly more cholesteryl ester (CE) synthesis than does control LDL (10.65 +/- 1.5 vs. 4.8 +/- 0.13 nmol.mg-1 cell protein.20 h-1; P less than .05). At LDL concentrations similar to those of plasma, the rate of CE synthesis in macrophages incubated with glycosylated LDL is more markedly enhanced than that observed in cells incubated with control LDL (3-fold increase). The marked stimulation of CE synthesis in human macrophages exposed to glycosylated LDL is paralleled by a significant increase in CE accumulation in these cells (P less than .001). The increase in CE synthesis and accumulation seem to be mediated by an increase in the degradation of glycosylated LDL by human macrophages. Glycosylated LDL enters the macrophages and is degraded by the classic LDL-receptor pathway in slightly smaller amounts than control LDL, but its degradation by pathways other than the classic LDL receptor or scavenger receptor is markedly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 May
PMID:Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocyte-derived macrophages. 312 28

It was about two decades ago that Chang proposed the use of microencapsulated islets as artificial beta cells. By using alginate-poly(L-lysine)-alginate membranes, biocompatible, durable capsules containing viable islet cells can be produced which are impermeable to cells and effector molecules of the immune system, thus providing a total protection to transplanted islets against rejection. The capsule wall contains 93% (w/w) water and can be classified as a hydrogel. Many hydrogels have gained general acceptance as being biocompatible materials. Microencapsulation of pancreatic islets for use as an artificial endocrine pancreas would not only obviate the need for immunosuppressive therapy but also has the potential to prevent the long-term complications of diabetes. Furthermore, the microencapsulation technique can be applied to other types of cells to produce antibodies or enzymes, and to treat a whole range of diseases requiring endocrine replacement therapy.
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PMID:Microencapsulation of pancreatic islet cells: a bioartificial endocrine pancreas. 313 33

A radioimmunoassay using antibody against glucitol-lysine was developed to quantitate glycated proteins in the lens of diabetic rats. The amount of glycated protein was expressed as molar equivalents of reduced glycated hippuryl lysine (GlcRED-Hip-Lysine). Significant differences (p less than 0.01) were found in the amounts of glycated protein in the lenses of rats with streptozotocin-induced diabetes (3.92 +/- 0.59 nmol/mg protein, n = 5), those with streptozotocin-induced diabetes treated with insulin (2.94 +/- 0.36 nmol/mg protein, n = 4) and normal rats (1.23 +/- 0.22 nmol/mg protein, n = 5). There was a significant correlation between the concentration of glycated protein in the lens and the HbA1c level at the end of the 12 week experiment (r = 0.957, p less than 0.001). These results indicate that glycation of lens protein is parallel with the severity of diabetes in rats.
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PMID:Specific radioimmunoassay of glucitol-lysine--application to lens proteins in streptozotocin-diabetic rats. 313 67

The nonenzymatic glycation of glomerular basement membranes (GBMs) from 14 diabetic and 19 nondiabetic human subjects was determined after boronic acid affinity and high-performance cation-exchange chromatography of their NaB[3H]4-reduced ketoamine adducts. The glucitol-lysine (Glc-Lys) and the glucitol-hydroxylysine (Glc-Hyl) content of diabetic GBM was found to be about twofold higher than that of nondiabetic samples (P less than .001). The content of these glycated amino acids did not correlate with age over the range examined (20-91 yr) or with the length of disease in diabetic subjects (2-16 yr). However, analyses of Glc-Lys and Glc-Hyl in calf and adult bovine GBM and lens capsules indicated that the levels of these glycated amino acids were several times greater in basement membranes from older animals. We also observed that guanidine-insoluble collagen of bovine GBM is more extensively glycated (approximately 4-fold) than primarily noncollagenous proteins that are extracted by this reagent. In all of the basement membranes examined, the percentage of glycation of lysine was greater than of hydroxylysine. Characterization of the components released by alkaline hydrolysis indicated that O-glycosylated hydroxylysine residues are nonenzymatically N-glycated to the same extent as those without an enzymatically attached carbohydrate unit. Our study indicates that more than a hundred times as many hydroxylysine residues are enzymatically glycosylated in human and bovine GBM as those containing the nonenzymatically formed ketoamine adduct.
Diabetes 1988 Aug
PMID:Nonenzymatic glycation of basement membranes from human glomeruli and bovine sources. Effect of diabetes and age. 313 65

Human erythrocyte proteins, incubated in vitro in the presence of various concentrations of glucose, undergo nonenzymatic glycosylation, as evidenced by thiobarbituric chemical procedure. In vitro incubation of normal blood cells with glucose gave rise to levels of protein-bound glucose as well as of anisotropy values similar to those found in diabetic patients. There was a linear correlation between the amount of lysine-bound glucose of total hemoglobin or membrane proteins and membrane fluidity (r = 0.904 and r = 0.902 respectively). The time course of the reaction is linear for the first hours, and the rate of glycation depends on the glucose concentration in the medium: at a glucose concentration of 28 mmol/l up to 37.4 nmoles of glucose is bound per mg of erythrocyte membrane proteins. Hyperbolic curvature of both time and glucose concentration dependencies were revealed for the glycosylation of hemoglobin and membrane proteins as well as for membrane fluidity alterations. As demonstrated by the finding of 5-hydroxymethylfurfuraldehyde augmentation, higher glucose concentrations result in elevated glycation of both blood cell membrane proteins and hemoglobin, followed by the increase of membrane diphenylhexatriene anisotropy, thus resembling by consequences the affection of blood proteins by chronic hyperglycaemia in diabetes mellitus.
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PMID:In vitro glycation of red blood cell proteins: high levels of glucose lower lipid fluidity of erythrocyte membranes. 322 58

We used furosine, which is derived from fructose-lysine and is a glycation product, to measure the extent of hair protein glycation in diabetic patients. We took hair samples that were 12 cm long, corresponding roughly to 1 year's growth. While the furosine levels in these samples correlated poorly with fasting plasma glucose (FPG) and with hemoglobin A1c (HbA1c) levels at the time of sampling, better correlations were observed between glycation and the year-long average values of FPG, HbA1c, and the conduction velocities in two peripheral nerves. The glycation levels in these samples may thus reflect the year-long average of the patient's blood glucose. Hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.
Diabetes Res Clin Pract 1988 Oct 14
PMID:Hair protein glycation as a long-term index of blood glucose in diabetics. 323 95

Protamines are cationic fish chromosomal proteins that retard absorption of isophane (NPH) insulins. Protamines are also administered in large doses for heparin neutralization in cardiac procedures. This study used a rapid enzyme-linked immunosorbent assay to examine frequency of protamine antibodies in diabetic and control populations. Antigen specificity of the IgG binding to protamine-coated plates was verified by competitive inhibition with other protamines, histone, glucagon, thyroid-stimulating hormone, arginine, and lysine. All antibodies tested cross-reacted completely with all protamines. Only 4 of 18 had any cross-reactivity with histones. None cross-reacted with the other inhibitors. In population surveys, 122 (38%) of 319 NPH insulin-treated diabetic subjects, 3 (8%) of 39 diabetic subjects treated with protamine-free lente insulins, and 5 (2.5%) of 202 normal control subjects had protamine antibody. No correlation was found between insulin and protamine antibodies. Because more than one-third of insulin-treated diabetic subjects have circulating IgG specific for protamine, they are potentially at risk for acute immunologic or anaphylactoid reactions when protamine is administered for heparin neutralization.
Diabetes 1988 Feb
PMID:Frequency and specificity of protamine antibodies in diabetic and control subjects. 329 13

Degradation of glomerular basement membrane in diabetic and nondiabetic rats was measured by incubating isolated basement membrane with a homogenate of glomeruli obtained from metabolically healthy rats. When diabetic basement membrane was used, there was a marked decrease in the amount of collagen-typical (hydroxyproline, hydroxylysine, glycine) and noncollagen-typical amino acids (proline, lysine, leucine) released in the supernatant of the incubation assay. A negative correlation was found between the amount of collagen-typical amino acids released by diabetic basement membrane and the duration of diabetes. The results indicate that the collagenous and noncollagenous peptides of diabetic basement membrane are less susceptible to proteolytic degradation than those of nondiabetic controls. This may be due to increased nonenzymatic glycosylation of diabetic basement membrane.
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PMID:Degradation of glomerular basement membrane in diabetes. I. Susceptibility of diabetic and nondiabetic basement membrane to proteolytic degradation of isolated glomeruli. 332 39

The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte anionic charge (RBCCh) and GAGs content in erythrocyte ghosts was shown. In view of the demonstration of a negative correlation between RBCCh and albuminuria after a lysine provocative test, these observations support the hypothesis that the onset of microalbuminuria in human diabetes is sustained by an alteration of glomerular charge and consequently of glomerular charge selectivity.
Diabetes 1988 Jun
PMID:Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria. 338 80

Carnitine (beta-hydroxy-gamma-N-trimethylaminobutyric acid) is required for transport of long-chain fatty acids into the inner mitochondrial compartment for beta-oxidation. Widely distributed in foods from animal, but not plant, sources, carnitine is also synthesized endogenously from two essential amino acids, lysine and methionine. Human skeletal and cardiac muscles contain relatively high carnitine concentrations which they receive from the plasma, since they are incapable of carnitine biosynthesis themselves. Since the discovery of a primary genetic carnitine deficiency syndrome in 1973, carnitine has become the subject of extensive research. It is now recognized that carnitine deficiency may also occur secondary to genetic disorders of intermediary metabolism as well as to a variety of clinical disorders, including renal disease treated by hemodialysis, the renal Fanconi syndrome, cirrhosis, untreated diabetes mellitus, malnutrition, Reye's syndrome, and certain disorders of the endocrine, neuromuscular, and reproductive systems. Administration of the anticonvulsant valproic acid and total parenteral nutrition may also induce hypocarnitinemia. In many instances, the physiological implications of secondary carnitine deficiency have not been resolved. However, evidence for a specific carnitine requirement for the newborn, especially if preterm, is accumulating. Moreover, carnitine administration may have a favorable effect on some forms of hyperlipoproteinemia. Carnitine, now recognized as a conditionally essential nutrient, is a significant factor in preventive medicine.
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PMID:Carnitine: an overview of its role in preventive medicine. 353 87


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