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)

Cataract is a long-term complication of diabetes mellitus. Diabetics have increased glucosamine levels and it is possible that the non-enzymic glycosylation of the lens structural proteins by glucosamine induces conformational changes in the lens that contribute to cataract formation. Aspirin and aspirin-like analgesics may protect against glycosylation. In this paper the binding of glucosamine to bovine lens proteins and the effects of aspirin, paracetamol and ibuprofen on this reaction were investigated. Significant binding of glucosamine to the lens proteins was found. Gel-chromatography indicated that beta H-crystallin was most reactive to the amino-sugar. Of the analgesics studied, aspirin was the most effective inhibitor of glycosylation, followed by the other anti-inflammatory drug, ibuprofen. Preincubation of the lens homogenate with aspirin was no more effective at decreasing binding of glucosamine than was simultaneous incubation with aspirin. Glutathione significantly inhibited glucosamine binding. Glucosamine is active in non-enzymic glycosylation but the reaction can be inhibited by agents thought to protect against cataract.
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PMID:The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. 275 89

Amino sugars such as galactosamine are hepatotoxic. It has been verified that toxic hepatitis induced by galactosamine is similar to that of CCl4 poisoning, and that both were inhibited by O2* scavengers. Fructosamine results from the union of glucose with the epsilon-amine of lysine. A test for fructosamine quantification is based on nitroblue tetrazolium (NBT) reduction, in which O2- is involved, the reduction being inhibited in the presence of superoxide dismutase (SOD). Given these facts, we attempted to elucidate if galactosamine and glucosamine reduce NBT and if that reduction is inhibited by SOD. This was confirmed. Subsequently, we incubated aminoacids (glycine, lysine, alanine) with glucose and galactose for 7 days and studied the action of the incubation products on NBT, using amino acids and sugars as controls. We found that NBT reduction increases proportionally to the length of incubation time of glucose/galactose with lysine, but not with other amino acids. Reduction of NBT by the Amadori compounds formed is inhibited by SOD. We suggest that oxygen radical generation by Amadori compounds must be taken into consideration as one cause of damage in diabetes of long duration.
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PMID:Oxygen radical generation by Maillard compounds. 283 94

A study on immunofluorescence of sialic acids in glomeruli from patients with diabetic nephropathy is described. Measurement of sialic acid in sera from 25 patients with diabetes mellitus was also performed. Renal biopsy specimens from 12 patients with diabetic nephropathy were stained with FITC-labeled antihuman IgG antiserum and rhodamine-labeled Triticum vulgaris (WGA) or Limulus polyphemus (LPA). These specimens were also stained with such reagents after treatment with neuraminidase, trypsin or citrate buffer. Both deposition of IgG and binding of WGA in the glomerular capillary walls were observed in all patients with diabetic nephropathy. The binding of WGA in the glomerular capillary walls in diabetic nephropathy was significantly increased compared with that in four normal renal tissues. However, the binding of LPA was hardly observed in the glomerular capillary walls of patients with diabetic nephropathy. The binding of WGA in the glomeruli was markedly decreased after treatment with neuraminidase although it was hardly decreased after treatment with trypsin or citrate buffer. The levels of sialic acid in sera from patients with diabetic nephropathy were markedly increased. It is suggested that accumulated substances in the glomerular capillary walls with an affinity for WGA are mainly composed of N-acetyl glucosamine and/or N-acetyl neuraminic acid in patients with diabetic nephropathy.
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PMID:Detection of glomerular sialic acids in patients with diabetic nephropathy. 328 77

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

In some patients with genetic forms of extreme insulin resistance, there is a marked decrease in the number of insulin receptors on the cell surface. We studied an insulin-resistant patient (RM-1) with the Rabson-Mendenhall syndrome. As judged by insulin-binding studies, Epstein-Barr virus-transformed lymphocytes from patient RM-1 exhibit a 90% decrease in the number of insulin receptors. Similarly, with either lactoperoxidase-catalyzed radioiodination of cell surface receptors or biosynthetic labeling of receptors with [3H]glucosamine, we demonstrated an 80-90% decrease in the number of insulin receptors in cells from patient RM-1. Previous studies have shown that the marked decrease in insulin receptors of the Rabson-Mendenhall patient is not due to accelerated receptor degradation. Therefore, we investigated the possibility that a slow rate of receptor biosynthesis might account for the 90% reduction of insulin receptors in cells from this patient. Insulin-receptor biosynthesis proceeds through a glycoprotein precursor with an apparent Mr of 190,000. It undergoes endopeptidase cleavage and further posttranslational processing to yield the mature 135,000- and 95,000-Mr glycoprotein subunits. We studied the biosynthesis of the 190,000-Mr precursor and mature receptor subunits by a pulse-chase labeling technique with [2-3H]mannose. The time course of insulin-receptor biosynthesis appeared normal in cells from patient RM-1, despite a 10-fold reduction in the number of receptors on the cell surface. Parallel pulse-chase experiments with either [2-3H]mannose or [35S]methionine yielded the same results regardless of which label was employed. Thus, the receptor precursor in the Rabson-Mendenhall patient seems to be synthesized at a normal rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jul
PMID:Insulin-receptor biosynthesis in cultured lymphocytes from an insulin-resistant patient (Rabson-Mendenhall syndrome). Evidence for defect before insertion of receptor into plasma membrane. 372 Oct 65

The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections.
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PMID:Diabetogenic action of streptozotocin: relationship of dose to metabolic response. 424 8

The plasma glycoprotein, dopamine-beta-hydroxylase (DBH), is present in markedly increased amounts in experimental, streptozocin (STZ)-diabetic rats, reaching a maximum at about the first week and maintaining a plateau for several months afterward. High glycemia values are observed simultaneously. Insulin treatment is observed to keep the glycemia and plasma DBH activity values at levels seen in control rats. The heterologous half-life of DBH in STZ-diabetic rats is significantly increased compared with that of control animals. The glucose analogue, 2-deoxy-D-glucose, has a similar effect on plasma DBH activity levels, eliciting high glycemia values. In STZ-diabetic animals, this increase is more significant, as if it were the additive effect of the two sugars. Other sugars that can compete for glycoprotein catabolic receptors can also modulate the plasma DBH activity levels. The lack of effect of galactose on DBH levels, together with the induced increase of DBH by alpha-methyl-D-mannoside and, to a lesser extent, by inulin, suggest an important rate for the mannose/glucose/N-acetyl glucosamine/fructose receptor in the catabolic clearance of DBH from plasma and explain the abnormal values seen for DBH in diabetes mellitus.
Diabetes 1984 Dec
PMID:Effect of diabetic hyperglycemia and other sugars on plasma dopamine-beta-hydroxylase activity. 620 84

35S-heparan sulfate (HS) metabolism by intestinal epithelial cells isolated from streptozotocin-diabetic and control rats was studied. In diabetic cells, a greater amount of 35S-radioactivity was incorporated into HS, however specific radioactivity of this polysaccharide was decreased. Studies into the distribution of sulfate residues in HS after selective deamination of the glucosamine units within the glycosaminoglycan (GAG)-chain, demonstrated that O-sulfate groups are preferentially located in relatively small deamination products: tetrasaccharides and disaccharides. A lower amount of radioactivity related to N-sulfate groups was found in HS from diabetic cells compared to that of control cells demonstrating that, in diabetes, less glucosamine residues within HS chains are subjected to N-sulfation. An increase in the percentage of 35-sulfate and in the percentage amount of uronic acid in tetrasaccharides of HS of diabetic cells indicated that a greater number of tetrasaccharides were generated by deaminative degradation of this HS. Since a decrease in the specific activity of uronic acid in disaccharides as in tetrasaccharides from HS of diabetic cells was observed, it is clear that the degree of O-sulfation of this HS is reduced. It is suggested, that "in vivo" changes in HS metabolism in diabetic intestinal epithelial cells lie in a disturbance in the degree of N- and O-sulfation of disaccharide units within the HS macromolecule.
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PMID:Evidence for diabetes-induced alterations in the sulfation of heparin sulfate intestinal epithelial cells. 623 64

A protocol has been developed for maintaining isolated rat adipose cells in primary tissue culture. Using this protocol, cells remain fully viable and responsive to insulin for at least 24 h, as assessed by measuring 3-0-methylglucose transport, lipogenesis from [U-14C]glucose, and the incorporation of [35S]methionine into total membrane protein. The acute insulin-induced internalization of its own receptor was then examined by biosynthetically labeling cells in culture with either [35S]methionine or [3H]glucosamine, maximally inducing receptor internalization with a 30-min incubation in the presence of saturating insulin, and preparing plasma and low-density microsomal membrane fractions by differential ultracentrifugation. Receptors were immunoprecipitated with anti-receptor antiserum, and the receptor subunits separated by NaDodSO4-PAGE under reducing conditions and analyzed by autoradiography. When cells not acutely treated with insulin are examined, both the 135K alpha- and 95K beta-receptor subunits are prominently labeled in the plasma membrane fraction, but only faintly labeled in the low-density microsomal membrane fraction. Following the induction of maximal acute receptor internalization, both subunits are decreased by 20-30% in the plasma membrane fraction and concomitantly increased in the low-density microsomal membrane fraction. However, the relative molecular weights and labeling intensities of the two subunits remain constant and correspond to those observed in the biosynthetically labeled human lymphocyte receptor. A minor band of Mr congruent to 190K is also labeled, but its labeling intensity is similar in the two membrane fractions from basal cells and does not change in response to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Jan
PMID:Insulin-induced internalization of the insulin receptor in the isolated rat adipose cell. Detection of both major receptor subunits following their biosynthetic labeling in culture. 636 Jul 64

Diabetic and normal cell lines from Chinese hamster kidneys were cultured in media containing 35SO4 and 3H-glucosamine. Glycosaminoglycans (GAG) were extracted and analyzed from the media, trypsin, and cell pellet by enzymatic and electrophoretic procedures. Significant increases in the hyaluronic acid content were noted in all three fractions of diabetic GAGs when compared with normals. In addition, an increased heparan sulfate content and decreased chondroitin sulfate amounts were noted in diabetic cell lines. These data suggest that in vivo changes in GAG types and amounts in diabetic kidneys seen by others may also be seen in cultured cells.
Diabetes 1981 May
PMID:Analysis of glycosaminoglycan from diabetic and normal Chinese hamster cells. 678 29


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