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)

This study examines the effects of various degrees of chemical modification of low-density lipoprotein (LDL) on its catabolism by various cell types. Moderate glucosylation of LDL does not alter its interaction with the high-affinity receptor present on human fibroblasts at concentration of 5-2000 micrograms LDL-cholesterol/ml. Only heavily glucosylated LDL (more than 12 lysine residues glucosylated per apolipoprotein B) or LDL glucosylated in the presence of Na(CN)BH3, i.e., conditions not expected to occur in diabetes, inhibit receptor-mediated internalisation and degradation. Moderately glucosylated LDL is also readily recognized by cultured rat hepatocytes and porcine endothelial cells. Human monocyte-derived macrophages accumulate cholesteryl ester when incubated with acetylated LDL for 12 days but no enhanced cholesteryl ester formation was found when native or glucosylated LDL (3.3 lysines glucosylated per apolipoprotein B) were used.
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PMID:Limited nonenzymatic glucosylation of low-density lipoprotein does not alter its catabolism in tissue culture. 392 87

Non insulin-dependent diabetes mellitus (Type II) is characterized by the loss of the acute insulin response to glucose. Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans. To evaluate the hypothesis that an increased sensitivity to these endogenous substances may play a role in defective insulin secretion in diabetes, we evaluated the effects of three blocking drugs upon the impaired insulin response to glucose in Type II diabetic subjects, as well as glucose-induced insulin secretion in normal humans. In diabetics, acute insulin responses to glucose were significantly increased by all the agents tested (naloxone, phentolamine and lysine acetylsalicylate), but only the cyclooxygenase inhibitor significantly augmented second phase insulin secretion and glucose disappearance rates. The combined infusion of the three agents caused a striking increase of the acute insulin response to glucose (response before: 3 +/- 2 uU/ml; after: 22 +/- 6 uU/ml, p less than 0.01). This was accompanied by a ninefold augmentation of the second phase of insulin secretion which was the result of a synergistic interaction between the three drugs (response significantly higher than the sum of single effects). In normals, insulin responses to glucose were also significantly increased by the combined infusions of the drugs, but to a significantly lesser extent than that of diabetics. This different degree of insulin potentiation between normals and diabetics under the infusion of the three agents persisted even when the prestimulus glucose level of normals was matched to that of diabetics by a glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired insulin secretion in human diabetes mellitus. Interactions between naloxone, phentolamine and lysine acetylsalicylate upon glucose induced insulin release. 393 37

In order to get an accurately specific determination of glycosylated hemoglobin (GHb-f), the furosine assay method, which can detect epsilon-amino-lysine-bound glucose, was investigated. A good correlation was found between GHb-f values obtained by this method and HbA1 values by conventional ion exchange column chromatography. It was, therefore, considered that this technique would be a new useful method for determining glycosylated hemoglobin.
Diabetes Res Clin Pract 1985 Dec
PMID:A specific method of glycosylated hemoglobin using furosine measurement. 393 17

Mammalian glucagon is thought to be highly conserved. Glucagons from pig, cow, human, rat, and hamster have identical amino acid sequences, whereas the amino acid contents of rabbit and camel glucagons are consistent with this 29-amino acid sequence. It had earlier been reported that guinea pig (GP) glucagon contains 40 amino acids. In the current study, glucagon was purified from two GP pancreata by a series of three HPLC steps after acid-alcohol extraction and acetone precipitation. GP glucagon is a 29-amino acid peptide that differs from other mammalian glucagons by substitution of Gln for Asp in position 21, Leu for Val in position 23, Lys for Gln in position 24, Leu for Met in position 27, and Val for Thr in position 29. In view of the marked changes in the COOH-terminal of GP glucagon, receptor binding studies were performed using both rat and GP liver membranes. Labeled synthetic porcine glucagon has similar binding in the two systems and its binding is inhibited to a similar degree by synthetic porcine glucagon, whereas GP glucagon is 10-fold less potent at inhibiting binding in both systems. This suggests that glucagon receptor binding sites in the GP are evolutionarily more conserved than is GP glucagon.
Diabetes 1986 May
PMID:Guinea pig glucagon differs from other mammalian glucagons. 395 84

This study reports the nonenzymatic glycation of plasma fibronectin in vivo in diabetic dogs and also in vitro by incubation of human plasma fibronectin with excess glucose. Although no difference is observed in the total plasma fibronectin level, the nonenzymatic glycation of fibronectin is increased 2.3-fold in inbred male beagle dogs made diabetic with alloxan in comparison with age-matched controls. The extent of non-enzymatic glycation of fibronectin is shown to be proportional to blood glucose levels. HPLC reverse-phase analysis of the hydrolyzed amino acids and glyco-amino acids from plasma fibronectin samples of normal and diabetic dogs show that nonenzymatic glycation occurs only on lysine residues. When purified human plasma fibronectin was incubated in vitro with 500 mM glucose, the extent of nonenzymatic glycation of fibronectin was observed to increase proportionately with time. Ligand binding assays conducted in solution with varying concentrations of 3H-heparin in the presence of a constant amount of normal or nonenzymatically glycated human plasma fibronectin gave virtually identical binding curves. However, the binding of 3H-heparin to normal fibronectin could be increased fourfold by the concomitant addition of normal gelatin (denatured calfskin collagen). If in vitro glycated fibronectin and/or in vitro glycated gelatin are added under this latter condition with 3H-heparin, there is a tremendous decrease in the expected heparin binding seen with normal levels of nonenzymatic glycation. Other experiments were performed to quantitate the binding of 3H-labeled fibronectin to gelatin-coated nitrocellulose filters. Nonenzymatic glycation of fibronectin in vitro resulted in markedly decreased binding of 3H-fibronectin to collagen.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Nonenzymatic glycation of fibronectin and alterations in the molecular association of cell matrix and basement membrane components in diabetes mellitus. 398 74

In this study metal-conjugated concanavalin A (Con A) and Bandieraea simplicifolia isolectin II (BSA II) have been applied to sections from kidneys of control rats and rats which had untreated diabetes for 70 days or for 200 days. Lectin binding was measured by atomic absorption spectrophotometric analysis of ferritin-iron or hemocyanin-copper. Con A binding increased significantly with diabetes; was totally blocked by alpha-D-mannoside; was not inhibited by fructose lysine; and was enhanced by NaHB4 preincubation. BSA II binding also increased significantly with diabetes.
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PMID:Lectin binding in the diabetic rat kidney. 404 12

Human very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoproteins (HDL2 and HDL3) were glycosylated in vitro by incubation with high concentrations of glucose and glucose-6-phosphate. Glycosylated lipoproteins showed enhanced mobility on agarose electrophoresis when compared to control lipoproteins, samples treated with glucose-6-phosphate being more strongly affected. Extent of glycosylation of LDL was determined using thiobarbituric acid, LDL incubated with glucose exhibiting degrees of glycosylation 15-117% in excess of control. LDL incubated with glucose-6-phosphate however, gave values similar to those obtained with control incubations. Amino acid analysis of protein hydrolysates prepared from VLDL and LDL fractions incubated with glucose revealed reductions of up to 53% in the levels of free lysine when compared to control lipoprotein samples. The appearance of 2 novel peaks, probably corresponding to glucosyllysine, was also observed. The effects seen with glucose-6-phosphate however, were not as marked as expected. None of the other amino acids measured were decreased. These data show that plasma lipoproteins can be glycosylated in vitro and that an indication of the degree of glycosylation (by glucose) may be obtainable using thiobarbituric acid. Amino acid analysis revealed that the probable binding site for glucose on the apoproteins are the lysine residues. Although glucose-6-phosphate also binds to lysine residues the effects produced by this agent on plasma lipoproteins may also involve other mechanisms requiring further investigation.
Diabetes Res 1985 Nov
PMID:Non-enzymatic glycosylation of plasma lipoproteins in vitro. 407 97

The cyclic hexapeptide, cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe), I, has been shown to have the biological properties of somatostatin. We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50-100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release. The hydroxyl group of tyrosine is seen to lend a 10-fold enhancement to the potency. Potency also is found to be correlated with hydrophobicity. II is found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The analog is found to be quite stable in the blood and in the gastrointestinal tract, but the bioavailability after oral administration is only 1-3%. The biological properties and long duration of II should allow clinical evaluation of the inhibition of glucagon release as an adjunct to insulin in the treatment of patients with diabetes.
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PMID:A super active cyclic hexapeptide analog of somatostatin. 614 33

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
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PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

The effect of nonenzymatic glycosylation on the susceptibility of fibrin to degradation by the specific fibrinolytic enzyme plasmin was evaluated using both a fibrin plate assay and a fluorogenic synthetic plasmin substrate assay. Data from both types of experiments demonstrate that nonenzymatic glycosylation reduces the susceptibility of fibrin to plasmin degradation. Acetylation and carbamylation have qualitatively similar effects, indicating that chemical modification of lysine amino groups is the underlying phenomenon responsible for the observed degradative defect produced by glucose. Experimental conditions that increased the rate of nonenzymatic protein glycosylation (higher monosaccharide concentration, glucose-6-phosphate) were associated with correspondingly greater degrees of resistance to degradation by plasmin. Such reduced degradation of nonenzymatically glycosylated proteins in vivo may contribute to the accumulation of fibrin and several other proteins observed in those tissues most frequently affected by the complications of diabetes.
Diabetes 1983 Jul
PMID:Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin. 622 31


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