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)

RT6.2 is a 26-kDa alloantigen expressed only on post-thymic T cells and attached to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. It has been reported that expression of RT6.2 in animal models may correlate with lymphopenia and genetically-induced insulin-dependent diabetes mellitus. Its physiological function is unclear. Since RT6.2 has significant amino acid identity with a GPI-anchored rabbit muscle NAD:arginine ADP-ribosyltransferase, RT6.2 was expressed in rat mammary adenocarcinoma cells and the ability of the expressed protein to catalyze ADP-ribose transfer reactions was examined. Cells transformed with the RT6.2 gene expressed NAD glycohydrolase activity that was released from intact cells by phosphatidylinositol-specific phospholipase C, consistent with its presence on the cell surface. A similar activity was not detected with vector-transformed cells. RT6.2 did not ADP-ribosylate simple guanidino compounds. The molecular weight of the phosphatidylinositol-specific phospholipase C-released NAD glycohydrolase, determined by SDS-polyacrylamide gel electrophoresis, was 22,000-24,000, in good agreement with that of native RT6.2. These results strongly suggest that the rat T cell alloantigen RT6.2 is a GPI-anchored NAD glycohydrolase.
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PMID:Expression of NAD glycohydrolase activity by rat mammary adenocarcinoma cells transformed with rat T cell alloantigen RT6.2. 814 25

The growth of 184 children with Type 1 diabetes was analysed using data collected prospectively in the Oxford district between 1969 and 1992. The overall mean height standard deviation score (Ht SDS +/- SD) at diagnosis was 0.35 +/- 1.05 which was significantly greater than the national standard of Tanner (1966). However, there is evidence of a secular trend in the heights of Oxford children over the last 20 years when compared with Tanner. When data from children with diabetes were compared with local controls, it was only the children aged 5-10 years at diagnosis who were taller (Ht SDS +/- SD, 0.58 +/- 1.14, versus 0.31 +/- 0.90, n = 73, p < 0.05). Those diagnosed under the age of 5 years (n = 37) were shorter (Ht SDS 0.12 +/- 0.93) and those diagnosed aged more than 10 years (n = 74) were similar in size (Ht SDS 0.22 +/- 0.98) to controls. These differences could not be explained by social class. Loss of height occurred between diagnosis and puberty, particularly in those diagnosed between the ages of 5 and 10 years. The pubertal growth spurt was blunted in all groups but this abnormality was more profound in the girls (mean peak height velocity SDS -1.09 +/- 1.02, p < 0.0005) than in the boys (mean peak height volocity SDS -0.5 +/- 1.14, p < 0.025). The mean final height SDS was -0.74 +/- 0.96 in those diagnosed < 5 years, 0.00 +/- 1.26 in those diagnosed between the ages of 5 and 10 years and 0.09 +/- 1.10 in those aged more than 10 years at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth during childhood and final height in type 1 diabetes. 820 Feb 4

An earlier study indicated that a chemically-modified non-antimicrobial tetracycline (4-de-dimethylaminotetracycline; CMT-1) can inhibit excess collagenase activity in the connective tissues of diabetic rats, however, the optimum oral dose and resulting serum concentration were not determined. In the current study, adult male Sprague-Dawley rats (body weight approx. 350 g) were made diabetic by streptozotocin injection and administered by oral gavage either 0, 1, 2, 5, or 10 mg CMT-1 per day. After 3 weeks of drug therapy, the rats were killed and gingiva, skin, and serum collected. The tissues were 1) extracted, partially purified and analyzed for collagenase activity using [3H-methyl] collagen as substrate and SDS-PAGE/fluorography; 2) extracted in neutral salt and dilute acid solutions (4 degrees C) to assess collagen solubility; and 3) analyzed for hydroxyproline to determine tissue (skin) collagen mass. Serum was analyzed for glucose and CMT-1 concentration, the latter by HPLC. Inducing diabetes dramatically increased both gingival and skin collagenase activity and reduced skin collagen mass by 69.8%. Increasing the oral dose of CMT-1 progressively increased the serum concentration of the drug from 0.6-6.5 micrograms/ml and progressively decreased the excessive collagenase activity in gingiva and skin (p < 0.01 vs untreated diabetics). Although skin collagen mass tended to be increased at all oral doses of CMT-1, only the 5 mg dose effect was statistically significant (p < 0.01). The diabetes-induced reduction in collagen solubility, a classic abnormality (reflecting excessive collagen crosslinking) of this disease, was also normalized by CMT-1 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemically-modified tetracycline normalizes collagen metabolism in diabetic rats: a dose-response study. 825 59

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus. 826 36

We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambda gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA1. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules, and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function.
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PMID:Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen. 832 4

Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D-xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Human kidney aldose and aldehyde reductases. 834 12

N-Acetyl-beta-D-glucosaminidase (NAG) can be found in kidney in high activity. By determination of this enzyme activity in urine nephropathies can be recognized reliably. We have measured this lysosomal enzyme in the urine (Colorimetric method by Noto) of 206 children suffering from diabetes mellitus to find out whether diabetic nephropathy can be detected as soon as possible. Additional beta 2-microglobulin (ELISA) was measured in urine, which is reabsorbed nearly complete in the tubulus. The several proteins in urine were identified by SDS-PAGE. A high excretion of beta-NAG was found in children and adolescents with a poor metabolic control (elevated HbA1c). There was no correlation between NAG activity, duration of the diabetes and the age of the children. An elevated excretion of beta-2-microglobuline could be found only in seven children with a duration of the diabetes about six years; their HbA1c levels were high. The SDS-PAGE showed a pattern of glomerular protein excretion according to the duration of the diabetes. However there was no significant correlation to the metabolic control. Only in four children we ascertained mixed proteinuria. The increasing levels of urinary NAG may represent the increasing severity of nephrotic damage by diabetes. The estimation of NAG levels in urine would seem to be reliable in the early detection of diabetic angiopathy also and may serve as an index of diabetic control independent of blood sugar levels.
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PMID:[N-acetyl-beta-glucosaminidase (beta-NAG) in urine: a parameter for early detection of diabetogenic nephropathy in childhood]. 836 78

Sugar alcohols have been reported to accumulate in retinal pigment epithelium (RPE) of diabetic animals. This finding has raised interest in the role of RPE in diabetes-associated retinal changes such as cystoid macular edema. To confirm the presence of aldose reductase in this tissue, the NADPH-dependent enzyme was purified to an apparent homogeneity from cultured human RPE cells, characterized, and its biochemical properties investigated. The induction of aldose reductase by hypertonic stress was also examined. The purification of aldose reductase was performed by a series of chromatographic steps which include gel filtration, affinity chromatography and chromatofocusing. Final purity achieved was monitored by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The kinetic properties and susceptibility to inhibition of the purified aldose reductase were essentially identical to aldose reductase purified from human placenta and kidney. In addition to aldose reductase, chromatofocusing demonstrated the presence of aldehyde reductase, another NADPH-dependent reductase. However, the amounts of aldehyde reductase present were much smaller than those of aldose reductase and the levels of aldehyde reductase appeared too small to contribute to the polyol production in the RPE cells. Culture of RPE cells in hypertonic medium containing 150 mM sodium chloride (600 mosmol total) increased both reductase activity, monitored with DL-glyceraldehyde as substrate, and immunoblot staining for aldose reductase. Chromatofocusing of RPE cells cultured in hypertonic media resulted in a prominent increase in the peak corresponding to aldose reductase compared to the peak height of cells grown in control medium. No increase in aldehyde reductase from RPE cells cultured in hypertonic medium was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldose reductase in human retinal pigment epithelial cells. 840 90

The vitreous is a neural extracellular space separated from the blood-vascular compartment by the blood-retinal barrier. Study of the appearance of serum proteins in this space have been carried out in rats with streptozotocin-induced diabetes mellitus, a condition associated with barrier dysfunction. A vitreous sampling technique that avoids contamination with surrounding tissue was employed. In rats 1 month after administration of streptozotocin (fasting serum glucose > or = 375 mg/dl), significant increases in vitreous protein were observed in the absence of discernible eye pathology. Two-dimensional isoelectric focusing and SDS-polyacrylamide gel analysis of the soluble fraction demonstrated 85 polypeptides, 28 of whose electrophoretic positions coincided with positions of serum polypeptides. The remainder were unrelated to serum polypeptide loci. Overall patterns of soluble protein from the vitreous of streptozotocin-injected and normoglycemic-uninjected control animals were virtually identical. Results support a system for selective transfer for certain proteins into the extraneural vitreous space as suggested by Chen and Chen (6).
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PMID:Protein levels in the vitreous of rats with streptozotocin-induced diabetes mellitus. 842 Jun 39

We have examined, by western immunoblot analysis, the sera of 16 insulin-dependent diabetes mellitus patients (IDDM) for the presence of autoantibodies against proteins extracted from islet-cell enriched preparations of normal human pancreata. A novel putative autoantigen recognized by late stage IDDM patients sera was identified, and its amino acid sequence was partially determined. Islets of Langerhans were partially purified by a modified collagenase digestion procedure, and subsequent protein extracts were fractionated by one-dimensional or two-dimensional polyacrylamide gel electrophoresis (1-D or 2-D SDS-PAGE). Immunoblot analysis revealed a 30-kD species which was recognized by 4 of 16 IDDM patients sera, but none of 16 normal sera. The 30-kD protein, appeared as a single band on 1-D SDS-PAGE, but was resolved on 2-D gel electrophoresis as several distinct protein species with different isoelectric points (pI's), ranging from 7 to 9. The amino terminal sequence of one such species was partially determined by microsequencing, and the second through the fourteenth amino acids were found to be identical to the corresponding sequence in human chymotrypsinogen. The fifteenth through the eighteenth amino acids were different from the known chymotrypsinogen sequence. This region corresponds with the site that is cleaved to activate chymotrypsinogen. Based on the size and sequence homology, this antigen appears to be related to chymotrypsinogen. We conclude that this 30-kD species may be an autoantigen in some late stage IDDM patients.
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PMID:IDDM patients' sera recognize a novel 30-kD pancreatic autoantigen related to chymotrypsinogen. 850 58


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