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)

The effect of immunomodulatory lectins on diabetes development following low-dose streptozotocin treatment in inbred mice was studied. All lectins administered had been shown previously to suppress immune reactivity. Among plant lectins concanavalin A but not Lens culinaris or wheat germ agglutinin partially suppressed hyperglycaemia following low-dose streptozotocin. A similar inhibitory effect was found for the staphylococcal enterotoxin B. Finally, administration of an immunomodulatory lectin from vertebrates, electrolectin, also had a beneficial effect on the course of the disease. These findings indicate that some lectins have a suppressive effect on Type 1 diabetes in an animal model.
Diabetes Res 1986 May
PMID:Suppression of low-dose streptozotocin-induced diabetes by immunomodulatory lectins. 374 41

Macrophage lectin receptors that recognize bacterial cell wall sugars are reduced in alloxan diabetic mice. This is in contrast to the expression of macrophage Fc (IgG2b) receptors which remains unaltered. Peritoneal macrophages, from diabetic and normal mice, were used as a source of accessory cells in an antigen dependent T cell proliferation assay with unopsonized Staph. epidermidis as the antigen. Uptake of this antigen in the absence of serum is via the macrophage lectin receptors. We have shown that diabetic macrophages induce a level of antigen dependent T cell proliferation to Staph. epidermidis. However the T cell response to Con A was similar with both normal and diabetic macrophages. We suggest that the observed defect in antigen presentation by diabetic macrophages is at the level of uptake of antigen. High glucose levels, such as those found in diabetes, down-regulate the lectin receptor, reduce phagocytosis of Staph. epidermidis and affect antigen presentation. This has important consequences in terms of the ability of diabetics to mount an effective immune response.
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PMID:Altered immune function in alloxan-induced diabetes in mice. 378 43

Insulin receptor autophosphorylation is the earliest recognizable event in insulin action subsequent to insulin binding. To determine if the postbinding hepatic insulin resistance of nonketotic diabetes mellitus could reside in an inability of insulin to stimulate insulin receptor autophosphorylation, we evaluated the ability of insulin to stimulate 32P incorporation into the beta subunit of lectin-purified rat liver plasma membrane insulin receptors. The data indicate that both the absolute plasma membrane insulin receptor autophosphorylation in response to insulin as well as the insulin dose-response relationship for autophosphorylation are normal in diabetic animals when expressed per microgram of protein or per unit of binding activity. The previous data from our laboratory indicates that hepatic insulin resistance in non-ketotic streptozotocin-induced diabetes mellitus is present despite normal to increased insulin binding, is selective, is reversible with insulin treatment and involves an inability of insulin to stimulate the release of the putative mediator of insulin action. We conclude, therefore, that the hepatic insulin resistance of nonketotic diabetes mellitus resides distal to insulin receptor binding and autophosphorylation and is reflected in metabolic events at or near the plasma membrane which may include the generation or release of the putative mediator of insulin action.
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PMID:Normal hepatic insulin receptor autophosphorylation in nonketotic diabetes mellitus. 389 Aug 53

The oligosaccharides maltose, maltotriose, mannotriose, and mannotetrose have been chemically attached to insulin molecules. Incubation of oligosaccharide and insulin at different molar ratios, with or without addition of cyanoborohydride, showed a nearly linear increase in carbohydrate attachment over time. The intravenous t1/2 of 125I-labeled sugar-insulin derivatives was identical to that of unmodified insulin (3.0 min). Biologic activity of these derivatives, assessed in rats by use of a blood glucose depression assay, did not differ significantly from control. These glycosylated insulin molecules are reversibly bound to the glucose-binding lectin Concanavalin A (Con A). Such sugar-insulin/lectin complexes serve as an insulin reservoir from which sugar-insulin molecules are displaced by glucose. Release of sugar-insulin molecules is a function of the particular sugar-insulin and of the ambient glucose concentration. Glucose displacement of glycosylated insulin complexed to Con A is in direct proportion to the amount of glucose present in the surrounding fluid. At each glucose concentration, the relative binding affinity of the maltotriose derivative is less than that of the mannotriose derivative, while the relative binding affinity of both maltotriose and mannotriose are less than that of the mannotetrose derivative. Prolonged incubation at 37 degrees C causes sugar-insulin, like unmodified insulin, to spontaneously aggregate into high-mol-wt, nondiffusable complexes. This aggregation phenomenon was found to be markedly inhibited when glycosylated insulins were synthesized utilizing partially sulfated insulin. Results from the studies described in this report provide the biochemical basis for a closed-loop, glucose-controlled insulin delivery system, utilizing glycosylated insulin complexed to Con A.
Diabetes 1983 Jun
PMID:Glycosylated insulin complexed to Concanavalin A. Biochemical basis for a closed-loop insulin delivery system. 635 78

The pretreatment of isolated islets of Langerhans with concanavalin A (Con A) completely blocks alloxan from suppressing the insulin release response to glucose. The lectin itself inhibits insulin secretion. This effect is dose dependent and reversible. Con A, however, has no protective action against the inhibition of glucose-induced insulin biosynthesis in islets exposed to alloxan. The protective action of Con A on alloxan toxicity is likely to be at the beta-cell surface at a membrane recognition site for glucose as a stimulus for secretion. The insulin biosynthetic effect of glucose appears to be mediated through a separate mechanism.
Diabetes 1984 Feb
PMID:Concanavalin A and alloxan interactions on glucose-induced insulin secretion and biosynthesis from islets of Langerhans. 636 70

Insulin receptors from rat hepatoma cells (Fao) and human placenta were partially purified by detergent solubilization and lectin purification. The insulin receptor preparations were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under reducing or nonreducing conditions. The proteins were transferred to nitrocellulose paper and the electrophoretic blots were treated with human anti-receptor autoantibodies, rabbit antibody to purified insulin receptor, or a monoclonal antibody to human insulin receptor. The nitrocellulose paper was then treated with 125I protein A or 125I second antibody followed by autoradiography. The rabbit polyclonal antiserum and one of the human autoantibodies recognized both the alpha (Mr = 135,000) and beta (Mr = 95,000) subunits after transfer from a SDS gel to nitrocellulose paper. On transfers from nonreduced gels, several high-molecular species were labeled ranging from Mr = 200,000 to Mr = 330,000. Similar high-molecular bands of the receptor were seen if highly purified human placental receptor, as well as partially purified receptor from rat or human origin, were used. As little as 0.1-0.5 microgram of pure receptor could be detected by this technique. Treatment of the receptor with neuraminidase (50 mU/ml) before gel electrophoresis resulted in a 50% increase in intensity of intact receptor and about a 70% increase in the labeling of the alpha-subunit of the receptor, but no change in labeling of the beta-subunit. The monoclonal antibody used, as well as two other human autoantibodies, did not recognize the receptor after transfer to nitrocellulose paper.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Oct
PMID:Visualization of the insulin receptor by immunoblotting. 647 60

Large glucagon immunoreactive substances, extracted from the fetal bovine pancreas and separated by gel filtration in the presence of 6 M guanidinium-hydrochloride, were submitted to lectin-sepharose affinity column chromatograph. Gel-filtered peak I (approximately 45 K delta) and peak II (approximately 10 K delta) interacted biospecifically with concanavalin-A- and wheat-germ-lectin-sepharoses, suggesting glycoproteins as possible constituents of large glucagon immunoreactive substances in extracts of the fetal bovine pancreas. The glucagon-like immunochemical identity of the lectin-sepharose-bound substances was further substantiated by binding to antiglucagon antibodies-sepharose and by characteristic proportional dilutions in the glucagon radioimmunoassay.
Diabetes 1982 Nov
PMID:Glycoprotein-like large glucagon immunoreactive species in extracts of the fetal bovine pancreas. 689 90

P-selectin is a transmembrane adhesion receptor specific to platelets and endothelial cells. It has an N-terminal lectin domain that recognizes specific carbohydrate moieties on monocytes, neutrophils and some other subsets of leukocytes. P-selectin is stored in granules and is expressed on the plasma membrane only after the cells are stimulated by vascular injury or during inflammation. Physiologically P-selectin is likely to be involved in the recruitment of leukocytes that promote wound healing and fight infection. There are many disorders in which the excessive recruitment of leukocytes is characteristic, including chronic inflammation, atherosclerosis, arthritis, diabetes, asthma and reperfusion injury. Because certain cancer cells also express the ligand for P-selectin it is possible that this receptor is involved in metastasis. To study the specific role of P-selectin in these pathological processes, we have prepared a mouse lacking P-selectin through gene targeting. Leukocyte interaction with the vessel wall is defective in these animals as leukocytes do not roll in the mesenteric venules and their extravasation at sites of inflammation and vessel injury is limited. We are testing these animals in models of the various diseases mentioned above in order to evaluate when the absence of P-selectin is beneficial.
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PMID:P-selectin knockout: a mouse model for various human diseases. 758 33

The inner ear of spontaneously diabetic WBN/Kob rats was functionally and morphologically examined in order to elucidate the relationship between diabetes mellitus and hearing impairment. At 3 months of age, WBN/Kob rats were non-diabetic, and their hearing function was normal. At 6-7 months of age, they showed decreased glucose tolerance and an increasing tendency toward urinary excretion of glucose without high plasma concentration of glucose, and were therefore judged to be pre-diabetic. They also displayed a significant elevation of hearing threshold in the auditory brainstem response, but showed little morphological and histochemical changes in the inner ear. At 12-13 months of age, they were spontaneously diabetic and showed a more apparent elevation of hearing threshold in auditory brainstem response than that in pre-diabetic animals. In addition, they displayed a marked decrease in the number of spiral ganglion cells and oedematous changes in the stria vascularis. The stria vascularis also showed a decrease in the intensity of staining with some lectins, i.e., wheat germ agglutinin, succinylated wheat germ agglutinin, Soranum tuberosum lectin, and concanavalin A. In conclusion, hearing impairment is induced by diabetes in the WBN/Kob rats first as an elevation of hearing threshold along with glucose intolerance; secondly, as a decrease in the number of spiral ganglion cells; and thirdly, as oedematous change of the stria vascularis with decreased intensity of lectin staining.
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PMID:Hearing impairment in WBN/Kob rats with spontaneous diabetes mellitus. 767 84

This paper is a study to identify the clinical significance of high-molecular-mass alkaline phosphatase (ALP:E:C..3.1.3.1.), ALP-lipoprotein-X complex (LP-X) and intestinal variant ALP. We used cellulose acetate and agarose gels and techniques including wheat germ lectin, cetavlon-diethyl ether, thermostatability, neuraminidase and L-phenylalanine to improve the electrophoretic separation of the alkaline phosphatase isoenzymes. Patients' serum samples were electrophoresed from a diverse group of individuals ill with cholestasis, neoplastic disease metastatic to the liver, hepatocellular carcinoma, cirrhosis, diabetes mellitus, and chronic renal disease. Agarose gels provided better separation of ALP isoenzymes than cellulose acetate gels. The results also indicated that high-molecular mass ALP is present in patient's serum in conditions associated with cholestasis especially caused by hepatic malignancy. High-molecular mass ALP was frequently found to co-exist with the liver isoenzyme and LP-XALP complex. The intestinal variant was identified in patients with malignancy, cirrhosis, chronic renal disease and diabetes mellitus. Intestinal ALP coexisted concomitantly with a variant intestinal ALP. Intestinal variant ALP is most likely composed of intestinal ALP attached to a cellular membrane-binding domain, or may be an artifact produced by neuraminidase incubation.
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PMID:Clinical significance of serum high-molecular-mass alkaline phosphatase, alkaline phosphatase-lipoprotein-X complex, and intestinal variant alkaline phosphatase. 804 46


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