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)

Using two different techniques, phenotyping and genotyping, we have studied allelic variation at amino acids 112 and 158 of the apolipoprotein E gene locus in 52 patients with insulin-dependent diabetes and in 58 non-diabetic controls. Phenotypes were determined by isoelectric focusing and immunoblotting of delipidated, neuraminidase-treated plasma. Genotypes were determined by using the polymerase chain reaction to amplify a 227 base pair fragment of the apolipoprotein E gene spanning both allelic sites. This was then digested with the restriction endonuclease CfoI and the alleles identified by polyacrylamide gel electrophoresis. Discrepancies between phenotype and genotype were observed in 16 (15%) of the individuals studied, 7 (13%) in the diabetics and 9 (17%) in the controls. From these results it is concluded that isoelectric focusing can lead to the erroneous assignment of apolipoprotein E phenotype even after pretreatment with neuraminidase. It is suggested that genotyping by DNA analysis is the method of choice in determining apolipoprotein E status.
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PMID:Apolipoprotein E phenotyping: a word of caution. 177 11

We have studied the combined effect of non-enzymatically glycosylated and desialylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycated LDL taken in the concentration percent, respectively. The effect of the same concentrations of glycated LDL treated with neuraminidase (desialylated-glycated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 micrograms/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycated (50 micrograms/ml) and desialylated (50 micrograms/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergetic effects of desialylated and glycated lipoproteins as well as LDL with both types of modification.
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PMID:Synergetic effect of desialylated and glycated low density lipoproteins on cholesterol accumulation in cultured smooth muscle intimal cells. 179 42

The role of sialidase in the depletion of glomerular sialic acid induced by diabetes has been investigated in uninephrectomized rats. Four months after streptozotocin administration, diabetic rats showed an enhanced urinary excretion of albumin and transferrin, which was associated with a decrease of sialic acid concentration in isolated glomeruli. Despite the sialic acid depletion, the glomerular sialidase activity was unchanged. These results indicate that the decreased glomerular sialic acid concentration observed in diabetic nephropathy might be caused by a disturbance of the sialylation of glomerular structures.
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PMID:Depletion of sialic acid without changes in sialidase activity in glomeruli of uninephrectomized diabetic rats. 179 17

In this study we demonstrate that haptoglobin, a serum glycoprotein secreted by the liver, has altered structure in the BB/Wor diabetic rat. SDS-PAGE of haptoglobin (a tetramer composed of two glycosylated beta-chains each containing two sites for Asn-linked oligosaccharides connected by disulfide bonds with two nonglycosylated alpha-chains) clearly shows that the beta-chain of haptoglobin from diabetic rats is smaller than normal, with a molecular mass of 39 instead of 40 kDa. Both acute and chronic diabetic rats exhibit the defect. Defective haptoglobin appears in the serum within 4 days of onset of the disease, but insulin therapy prevents the defect. Removal of Asn-linked oligosaccharides with peptide: N-glycosidase F from Flavobacterium meningosepticum abolished the size difference between the beta-chains from normal and diabetic haptoglobin, with the molecular mass in both cases shifting to 30 kDa. Haptoglobin from both normal and diabetic rats was resistant to digestion by endoglycosidase H from Streptomyces griseus, which cleaves high mannose-type chains. Removal of sialic acid with neuraminidase treatment resulted in a reduction in the molecular mass in both cases, but without eliminating the size difference between the two. These results demonstrate that haptoglobin from diabetic BB/Wor rats contains a structural abnormality which correlates with onset of the disease. The defect is most likely due to an alteration in Asn-linked oligosaccharides, probably involving a change in the neutral sugars of complex-type oligosaccharide chains. This finding represents the first example of an altered Asn-linked oligosaccharides in diabetes.
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PMID:Diabetic BB/Wor rat haptoglobin exhibits a probable structural abnormality in Asn-linked oligosaccharides. 202 25

Kidney cortex sialic acid level, sialidase and sialyltransferase activities have been measured in spontaneously diabetic BB rats and in streptozotocin-diabetic rats (STZ). In untreated diabetic BB rats, at the onset of the disease, sialidase specific activity was found to be increased by 21% when compared with diabetes-resistant BB controls (P less than 0.05) whereas sialyltransferase activity was not significantly modified and bound sialic acid concentration was diminished (P less than 0.05). In diabetic BB rats submitted to a minimal insulin therapy, during 3 months of disease, sialidase activity and sialic acid concentration were similar to those of Wistar age-matched controls. In STZ-diabetic Wistar rats, sialidase specific activity was increased by 76% after 5 months of disease when compared to age-matched Wistar controls (P less than 0.01); in contrast, specific sialyltransferase activity was decreased by 21% (P less than 0.05); these enzymatic alterations were associated with a decrease in bound sialic acid concentration (P less than 0.01); 1 month's insulin therapy, started 4 months after onset of the disease, normalized sialidase activity but had no effect on sialyltransferase activity and sialic acid concentration; treatment with sorbinil prevented cataract development but had no effect on sialidase activity whereas it emphasized the decrease in sialyltransferase activity and sialic acid concentration. The disturbances in the enzyme activities concerned with sialoglycoconjugate metabolism observed in experimental and spontaneous diabetes may be responsible for the decreased bound sialic acid content observed in the rat kidney cortex.
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PMID:Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats. Influence of insulin and sorbinil treatments. 220 Apr 8

Insulin receptor-specific polyclonal antipeptide serum was generated against a synthetic pentadecapeptide (residues 657-670) of the deduced amino acid sequence of human insulin proreceptor cDNA for use in the analysis of insulin receptors in the retina. The affinity-purified antibodies recognized peptide antigen but not keyhole limpet hemocyanin as determined by dot blot analysis and solid phase radioimmunoassay. Addition of either synthetic peptide or the affinity-purified serum had no effect on 125I-insulin binding to placental membranes or to cells in culture. alpha-Subunits of approximately 125 kDa from human placental membranes and liver membranes were labeled by immunoblot analysis with this antiserum. In membranes isolated from human retina and brain, two classes of alpha-subunits of approximately 125 and 115 kDa were detectable. The 115-kDa subunit was neuraminidase resistant whereas the 125-kDa subunit was digested to a band of 115 kDa, indicating that these bands represent peripheral and neuronal receptors, respectively. Analysis of human retinas obtained from type I diabetic donors revealed an increased level of neuronal receptor as compared with normal retinas. These data indicate that human retina expresses neuronal insulin receptor subtypes that are up-regulated in diabetes.
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PMID:Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor alpha-subunit. Up-regulation of neuronal insulin receptors in diabetes. 221 78

The degree of apo E sialylation in VLDL from serum of diabetics and controls was determined by densitometric scanning of the pherograms after isoelectric focusing of the VLDL proteins including treatment with neuraminidase. The distribution pattern of sialylation within the groups of patients and controls followed a Gaussian type. A significantly elevated level of sialylated apo E could be demonstrated in IDDM and NIDDM as compared to the controls. No correlation was found between the apo E phenotype and the diabetic state. From the correlation analysis including the parameters degree of sialylation, age, duration of diabetic state, and blood glucose pattern no significant results were obtained except a significant but only week correlation (r less than 0.3) between sialylation, age, and blood glucose in IDDM patients. Possible consequences of the elevated apo E sialylation in diabetes mellitus are discussed.
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PMID:[The sialylation rate of apolipoprotein E in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus]. 233 Jul 43

To investigate the autoimmune pathogenesis of spontaneously occurring diabetes mellitus in BB rats, spleen cells of newly diagnosed diabetic BB rats were fused with mouse myeloma cells. Hybridoma supernatants were screened for antibodies by indirect immunofluorescence and by 51Cr-release assays using the RINm5F rat insulinoma cell line. One clone, E5C2, produced an IgM kappa antibody that was cytotoxic for RINm5F cells, but not for other rat cell lines nor for primary rat islet cells. However, treatment of primary rat islet cells with neuraminidase exposed surface antigens and rendered the cells susceptible to complement-mediated lysis by antibody E5C2. Using immunostaining of glycolipids separated by thin-layer chromatography, hapten inhibition assays with defined carbohydrates, and Western blots, the antigens recognized by E5C2 on RINm5F cells were identified as glycoproteins with molecular weights of 60,000 and 68,000. The antibody recognizes a carbohydrate antigen containing the sequence Gal beta 1-4GlcNAc-R, which on RINm5F cells is predominantly hidden by covalently bound sialic acid. These studies raise the possibility that hidden antigenic determinants on islet cells exposed by a variety of means may be the target of autoimmune attack.
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PMID:Pancreatic islet cell surface glycoproteins containing Gal beta 1-4GlcNAc-R identified by a cytotoxic monoclonal autoantibody. 243 47

Measurement of sialic acid and acute phase reactant (APR) proteins in sera of patients with diabetic nephropathy was performed. Twenty-six patients with non-insulin-dependent diabetes mellitus (NIDDM) were examined. The levels of sialic acid in sera, with or without treatment of neuraminidase, were measured by the thiobarbiturate method. The levels of alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AG) or alpha 2-macroglobulin (alpha 2-MG) were measured by laser nephelometry. The levels of sialic acid or APR proteins in sera of patients with diabetic nephropathy were increased markedly. There was a significant correlation between the levels of sialic acid and those of alpha 1-AT in sera of patients with NIDDM. The mobility of alpha 1-AT in sera of patients with NIDDM treated with neuraminidase was decreased markedly in the immunofixation test. It is suggested that the increase of APR proteins in diabetic sera is mainly composed of sialic acid in patients with NIDDM with or without nephropathy.
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PMID:Measurement of sialic acid and acute phase reactant proteins in sera of patients with diabetic nephropathy. 246 54

The target antigens of islet cell antibody (ICA) have not been clarified. We tried to modify the antigen in human pancreatic tissues and characterize the ICA with immunohistochemical methods. Human pancreatic tissues were treated with periodate (A), borohydride (B), neuraminidase (C), methanol (D), chloroform-methanol (E), or protease (F) to modify the antigens, and stained by an immunofluorescent method using ICA-positive sera from five Japanese insulin-dependent diabetes mellitus (IDDM) patients. In all sera the fluorescence of islets disappeared or waned after A, C, D, and E, and did not change after F. The disappearance or loss of fluorescence induced by A was recovered after B. It is, therefore, suggested that one of the antigens of ICA in Japanese IDDM patients is the sialic acid residue of glycolipid.
Diabetes Res Clin Pract 1989 Apr 01
PMID:Target antigen of islet cell antibody in Japanese insulin-dependent diabetes mellitus. 265 66


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