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 examined the clinical usefulness determined by polyacrylamide gel electrophoresis, followed by reaction with peroxidase-coupled lectins using urinary glycoproteins for diabetic nephropathy in 20 patients with diabetes mellitus. Lectins used were Triticum vulgaris (WGA), Phaseolus vulgaris (PHA-E4), Dolichos biflorus (DBA), and Lens culinaris (LCA), which have high affinity for beta 1----4N-acetyl-D-glucosamine (GlcNAc beta 1----4GlcNAc), N-acetyl-D-galactosamine (GalNAc), alpha-galactosamine (alpha-GalNAc), and alpha-mannose (alpha-Man) residues, respectively. Electrophoretic patterns of urinary glycoproteins clearly showed the presence of lectin-reactive glycoproteins with molecular weights lower than that of albumin. The molecular weight of the main bands reacted with WGA, PHA-E4 or LCA were 50,000 and 38,000, and increased with the progress of diabetic nephropathy. WGA reacted strongly with many glycoproteins having a wide range of molecular weights. LCA and PHA-E4 reacted preferentially with glycoproteins of molecular weights glycoproteins of molecular weights lower than 50,000, but no reaction was observed by DBA. These results suggest that low molecular urinary glycoproteins have abundant carbohydrate residues such as GlcNAc beta 1----4GlcNAc, GalNAc, and alpha-Man. The excretion of low molecular weight glycoproteins with high affinities for some lectins suggests functional impairment in diabetic nephropathy.
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PMID:[Electrophoretic analysis of urinary glycoproteins in diabetic nephropathy using peroxidase-lectins]. 248 79

Postbinding defects in insulin action were described previously in cultured fibroblasts from six patients with lipoatropic diabetes. To define the contribution of the insulin receptor tyrosine kinase in these defects, we studied autophosphorylation and kinase activity of lectin purified receptors from these six patients and six normal cell lines. The patients' insulin receptors, prepared by precipitation with polyethylene glycol, had normal insulin binding characteristics and autophosphorylation properties, but a 56% decrease in the tyrosine kinase activity toward an exogenous substrate. To identify more subtle qualitative defects in autophosphorylation, insulin receptors were sequentially immunoprecipitated and analyzed for their phosphoaminoacid content. The phosphorylated receptors precipitated with an antiphosphotyrosine antibody contained labeled phosphotyrosine, whereas those in the supernatant, when further precipitated with an antireceptor antibody, contained only phosphoserine. Under these conditions, the insulin-stimulated autophosphorylation of tyrosine was significantly decreased by 54% in the patient receptors compared to normal subjects' receptors. In addition, insulin-like growth factor-I stimulation of autophosphorylation of its receptor was reduced by 59% in the patients' cells compared to those from normal subjects. We conclude that fibroblasts from patients with lipoatropic diabetes have defects in the tyrosine kinase activity of their insulin and their insulin-like growth factor-I receptors that might give rise to the in vitro hormone resistance and be related to the in vivo hormone resistance that occurs in these patients.
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PMID:Tyrosine-kinase defect of the insulin receptor in cultured fibroblasts from patients with lipoatropic diabetes. 254 88

Because successful human islet transplantation requires large quantities of viable islets that must be separated from the highly immunogenic exocrine tissue and because handpicking is too time-consuming and laborious to be clinically relevant, a new approach for solving this problem has been established in rat models. It is based on the principle that magnetic microspheres (MMSs) coupled to lectins with binding specificity for the exocrine tissue portion are trapped in an electromagnetic field, thus providing effluent islets of a high degree of purity. In this study our aim was to adapt this principle to human islet preparations. In this context our prime interest was focused on a lectin suitable for human pancreatic tissue. Of 19 different lectins tested, only 1, Wisteria floribunda agglutinin (WFA), is suitable, as shown by immunofluorescence, MMS-lectin binding, and magnetic separation.
Diabetes 1989 Jan
PMID:New principle for large-scale preparation of purified human pancreas islets. 264 40

We have studied the comitogenic activity of IL 1 produced by cultures of mononuclear adherent cells obtained from Diabetes Mellitus (DM) type II or non insulin dependent diabetic patients. This activity was measured by the incorporation of 3H Thymidine into cultures of C3H/HeJ mice thymocytes in the presence of phytohemagglutinin (PHA). We have observed that IL 1 from patients with DM type II did not produce a synergistic effect with PHA, since the lymphoproliferation levels were similar to those obtained in the absence of this lectin. This lack of comitogenic activity (P less than 0.001) in relation to the response obtained with IL 1 from normal subjects plus PHA, could be due to the release of one or several soluble substances capable of blocking glycosylated receptors to mitogens or of impairing the cellular activation process.
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PMID:[Evaluation of the interleukin 1 production by adherent cells in patients with diabetes type II]. 269 36

It has been demonstrated in in vivo and in vitro experiments that high-fat (HF) feeding causes insulin resistance. To elucidate the mechanism for this effect, we have measured the kinase activity of the insulin receptor purified from livers of HF-fed rats that showed impaired insulin action in isolated rat adipocytes. In adipocyte experiments, HF feeding led to a 65% decrease in the maximal response stimulated by insulin in a 2-deoxyglucose uptake study. Although insulin binding to adipocytes of HF-fed rats also decreased to 50% of control due to decreased binding affinity, the postbinding defect should be accounted for by decreased insulin action in view of the presence of spare receptor. In contrast to adipocytes, insulin binding to the lectin-purified insulin receptor from livers showed no difference in receptor-binding affinity between HF-fed and control rats. Insulin-stimulated phosphorylation of the beta-subunit of the insulin receptor was decreased to almost 50% throughout the entire dose-response curve. The study of glutamine-tyrosine (4:1) phosphorylation by the insulin-receptor kinase showed results similar to those of the autophosphorylation study. These results suggest that an HF diet causes insulin resistance by affecting insulin-receptor kinase, which plays an important role in transmembrane signaling between insulin binding and insulin action.
Diabetes 1988 Oct
PMID:Alteration of insulin-receptor kinase activity by high-fat feeding. 284 8

Treatment of male C57BL6/J mice with low doses of streptozotocin causes the development of diabetes. Infiltration of pancreatic islets by immune cells and the concomitant loss of beta islet cells can be prevented by immunosuppression. We now report that i.v. administration of islet homogenate 13 d prior to low dose streptozotocin treatment largely protects from development diabetes. Homogenates from liver, kidney or exocrine pancreas were without effect. The suppressive activity was isolated partially from mouse islets as well as from a rat insulinoma cell line. After gelchromatography the suppressive activity was found in the 600 kD fraction. The relevant substance appears negatively charged and does not bind to lentil lectin or concanavalin A.
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PMID:Administration of a 600 kD molecular fraction from pancreatic islets suppresses immune mediated diabetes in mice. 307 28

BB rats are prone to develop an autoimmune form of insulin-dependent diabetes mellitus (IDDM) and thyroiditis. Development of autoimmunity is thymus dependent. Previous studies have shown that BB rats lack a population of T cells bearing the RT6 antigen and have very low numbers of suppressor/cytotoxic T cells. In this study, we confirm that BB rats have decreased numbers of phenotypic T suppressor/cytotoxic (Ts/c) cells (OX19+, OX8+ cells) in their lymphoid organs. Moreover, we find that the phenotypic Ts/c cells of BB rats lack apparent cytotoxic activity. These T cells fail to kill allogeneic target cells in a cell-mediated lympholysis assay and fail to generate lectin-dependent cytotoxicity. The addition of interleukin 2, gamma-interferon, and other lymphokines to cultures of BB T cells does not induce functional cytotoxic T lymphocytes. We find that the activated T cells of newly diabetic rats are incapable of killing major-histocompatibility-complex-matched islet cells, despite the ability of these cells to cause IDDM in passive transfer experiments. We conclude that autoimmune disease occurs in BB rats in the absence of functional cytotoxic T cells.
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PMID:Autoimmunity-prone BB rats lack functional cytotoxic T cells. 313 Oct 22

Earlier histochemical findings from our laboratory have shown that a lectin (agglutinin) from Griffonia simplicifolia, which reportedly binds to terminal N-acetylglucosamine residues in glycoconjugate oligosaccharides also shows affinity for glycogen. In the present study, the lectin was conjugated to horseradish peroxidase and applied to paraffin sections of kidney from streptozotocin-diabetic rats, insulin-treated and untreated, and age-matched control rats. Griffonia simplicifolia agglutinin II detected glycogen in cortical ascending thick limbs of untreated diabetic rat kidneys as early as 24 h following injection of streptozotocin. The number of stained cells increased steadily so that by day 14 of diabetes the lectin reacted with nearly all of the cells lining ascending thick limbs in the cortex and adjacent outer stripe of the outer medulla. Glycogen was never identified in the inner medullary stripe. Comparison of Griffonia simplicifolia agglutinin II and periodic acid-Schiff staining revealed that periodic acid-Schiff could not clearly detect glycogen until 14 days following injection of streptozotocin, which substantiated earlier claims that Griffonia simplicifolia agglutinin II might be a more sensitive indicator of glycogen than periodic acid-Schiff. The distribution of glycoconjugate containing terminal N-acetylglucosamine stainable with the lectin was unchanged in diabetic kidneys. Griffonia simplicifolia agglutinin II served in the present study to further characterise the sequence of abnormal glycogen accumulation in streptozotocin-diabetic rat kidneys. In addition, it was shown that the lectin's ability to antedate periodic acid-Schiff detection of glycogen has utility in histochemical investigations in diabetes.
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PMID:Lectin detection of renal glycogen in rats with short-term streptozotocin-diabetes. 342 97

The continuously growing, insulin-secreting cell line RINm5F does not respond to glucose with increased rates of insulin secretion and cell proliferation. The possibility that retinoic acid, which acts as a differentiating agent in several cell systems, could induce such responses to glucose has been investigated. Retinoic acid (10(-6)-10(-5) mol/l) failed to affect the cell viability, cell proliferation, 3H-thymidine incorporation or the DNA contents of the cultured RINm5F cells, irrespective of the glucose concentration of the culture medium. The insulin release was not affected either by glucose or by retinoic acid. Higher concentrations of the drug (10(-4) mol/l) proved toxic to the cells. The incorporation of 3H-mannose and 3H-glucosamine into TCA precipitable material of the RINm5F cells was strongly decreased by an increased glucose concentration of the medium. The incorporation of 3H-mannose, but not that of 3H-glucosamine, into macromolecules which could be precipitated with Concanavalin A or wheat germ lectin was diminished by retinoic acid (10(-5) mol/l).
Diabetes Res 1986 May
PMID:Effects of retinoic acid on growth, insulin secretion, and hexose incorporation into macromolecules of a continuously growing, insulin-secreting cell line (RINm5F). 352 18

A large-molecular-weight proinsulin-immunoreactive protein fraction was obtained from an extract of fetal bovine pancreases by gel filtration in 6 M guanidine-1 M acetic acid. Concanavalin A-Sepharose-affinity column chromatography of the large-molecular-weight fraction yielded a discrete alpha-methyl-mannoside-displaceable immunoreactive peak that also displayed N-acetylglucosamine-specific binding to wheat germ lectin-Sepharose. Chemically tritiated and radioiodinated lectin-reactive proteins interacted specifically with antibodies to insulin and bovine proinsulin. Immunochemically purified (reaction with antibodies followed by separation of antigen-antibody complexes on protein A-Sepharose) radiolabeled lectin-reactive proteins were analyzed by gel filtration in guanidine-acetic acid and by sodium dodecyl sulfate polyacrylamide gel electrophoresis after disulfide bond-cleavage treatments. Results from these studies suggest the existence of an approximately 67,000-Mr glycoprotein that contains antigenic domains common to proinsulin and insulin.
Diabetes 1987 Apr
PMID:Evidence for presence of proinsulin-immunoreactive glycoprotein(s) in fetal bovine pancreatic extracts. 354 49


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