Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal sucrose hydrolysis and absorption of monosaccharide products was studied in vivo utilizing the segmental perfusion technique in diabetic and control rats. The proximal jejunum was perfused with 20 mM sucrose, 140 mM NaCl and 0.5% PEG with 14C-PEG, as the nonabsorbable marker. Rates of sucrose hydrolysis and adsorption of monosaccharide products (fructose, and glucose) were determined. There were no statistically significant differences between the diabetic and control rats. This indicates that the previously reported increase in sucrase activity in diabetes does not correlate with enhanced rates of sucrose hydrolysis. Several possibilities for the interpretation of these results are discussed.
 ...
PMID:Intestinal digestion and absorption of sucrose in experimental diabetes. 102 Jun 13

RIA methodology is used widely to measure proinsulin in human serum. However, some RIAs lack the sensitivity necessary to quantify proinsulin in unextracted serum and require long incubation periods. We developed an RIA with a sensitivity of 3.5 pM that permits the routine measurement of proinsulin in less than 48 h. This was accomplished by using a nonequilibrium binding reaction at room temperature and PEG-assisted second antibody precipitation as the method for separating bound and free proinsulin. We obtained a specific antiproinsulin antibody by absorbing the initial goat antiserum with human C-peptide-agarose. Proinsulin produced 50% displacement of tracer at 25.6 pM, whereas both human insulin and C-peptide failed to displace tracer at concentrations as high as 1 microM. We evaluated several cleaved derivatives of proinsulin for cross-reactivity with the antibody. B-chain-C-peptide cleaved derivatives (less than or equal to 50% cross-reactivity) were more potent than A-chain-C-peptide cleaved derivatives (less than 5% cross-reactivity). However, all derivatives cleaved in the region from 56-60 failed to cross-react with the antiserum. These data indicate that a major antigenic determinant is present on the C-peptide region of proinsulin adjacent to the A-chain-C-peptide junction. After administration of an oral glycemic challenge, the mean fasting serum concentration of proinsulin in normal adults rose from 4.1 +/- 0.28 to 23.6 +/- 3.8 pM. We found a significant difference in the proinsulin concentrations in 6 adults before and after a glycemic challenge when two different antibodies were used in the RIA.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Sep
PMID:A rapid and sensitive radioimmunoassay for the measurement of proinsulin in human serum. 149 62

The involvement of radical reactions in the ageing process, physiological as well as pathological, is well demonstrated. It is accepted that alloxan cyto-toxicity is linked to a production of hydroxylated free radicals and that a substance preventing the development of alloxanic diabetes possesses scavenger properties. The objective of this work was to demonstrate, in this model, the anti-radical effect of 3 molecules recommended in the treatment of cerebral insufficiency and a reference substance (+)-catechin. We observed a protective action with catechin (P less than 0.05) at the highest dose (100 mg/kg). PEG alone was moderately active but comparison of PEG-alloxan and PEG-exifone-alloxan showed a highly significant difference (P less than 0.001) at the two highest doses (60 and 120 mg/kg). Piracetam (200 and 400 mg/kg) and vinburnine (7.5 and 15 mg/kg) were inactive. Under these experimental conditions, exifone demonstrated remarkable anti-radical properties.
 ...
PMID:Comparative evaluation of scavenger properties of exifone, piracetam and vinburnine. 280 30

Insulin antibodies are known to interfere with the radioimmunoassay of insulin. We tested intravenous glucose tolerance on 25 insulin autoantibody-positive (IAA+) patients and 25 IAA- controls, who were matched for sex, age, and body mass index, to establish if IAA could also interfere with insulin assay. Insulin content was measured in untreated serum, serum precipitated with polyethylene glycol (PEG, free insulin), and serum extracted with acid and precipitated with PEG (total insulin). The mean untreated first-phase insulin response (I1 + 3) for IAA+ patients was 172 +/- 67.3 mU/L, significantly higher than the mean control value of 108 +/- 47.5 (P less than .001). After PEG precipitation, mean I1 + 3 in the patient group fell significantly to 105 +/- 48.4 mU/L (P less than .001), but the control value was unchanged (104 +/- 45.5). The mean percentage fall after PEG precipitation was 36.9% (patients) and 2.9% (controls) (t = 8.3, P less than .001). There was a strong correlation between the IAA titer and the interference in the insulin assay (r = .81). After total insulin extraction of IAA samples, there was a significant fall in mean I1 + 3 to 134 +/- 55.4 mU/L (P less than .001), but the control value was unchanged. IAA can significantly falsify insulin measurement, and care must be taken in the interpretation of insulin-release tests when IAA is present.
Diabetes 1988 Oct
PMID:Insulin autoantibodies and insulin assay. 304 70

After ingestion of metformin, a drug of the biguanide class, there are gastrointestinal effects in the form of nausea and vomiting, and about 30% of the drug is recovered in feces. The purpose of this work was to explain these two phenomena. Two sets of experiments were carried out. Study I evaluated the gastroduodenal (GD) absorption in six healthy volunteers by means of an intubation method, employing a twin-lumen tube introduced into the intestine and another into the stomach. Metformin 1 g was introduced into the stomach with a homogenized meal containing a non-absorbable marker, 14C-PEG 4000; another marker, PEG 4000, was perfused continuously into the duodenum at the ampulla of Vater. Samples of GD contents were collected every 15 min during 4 h. Metformin was poorly absorbed from the stomach, about 10% over a 4-h period. It did not modify the gastric emptying of a meal but induced a duodeno-gastric reflux in five out of six subjects. About 20% of the amount of drug emptied from the stomach were absorbed from the duodenum. The delivery process was the rate-limiting factor for metformin absorption from the duodenum. The AUC/24 h increased as the absorption rate from the duodenum increased. Study 2 investigated in six healthy volunteers, using another intestinal perfusion technique, the jejunal and ileal absorption of metformin. Metformin 400 mg in saline solution was perfused, over a 2-h period, below an inflated balloon, directly into either the jejunum or the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1988 Feb 19
PMID:Metformin in the digestive tract. 335 23

Chinese hamster ovary fibroblasts, as model cells, have been microencapsulated in a hydroxyethyl methacrylate-methyl methacrylate copolymer (HEMA-MMA) by interfacial precipitation. The polymer containing approximately equal to 75 mol% HEMA, dissolved in polyethylene glycol 200 (PEG 200) was coextruded with the cell suspension (4-6 X 10(5) cells/ml in the alpha-MEM with 10% foetal calf serum +/- Ficoll 400/PBS) through a concentric needle assembly. Polymer solution droplets, containing cells, were blown off the end of the needle assembly by a coaxial filtered air stream into a nonsolvent bath containing phosphate buffered saline (PBS) with 5 ppm Pluronic L101, overlaid with hexadecane. The nascent capsules hang at the hexadecane/PBS interface while the solvent is extracted into the aqueous nonsolvent, to precipitate the polymer around the cells. The resultant capsules were 500 microns-1 mm in diam. with a microporous sponge-like interior, and also very tough and flexible. The cells survived encapsulation based on subculture ability, retention of some fluorescein diacetate (FDA) activity over 5 d and direct light microscopic evidence of cell growth over 10 d after histological sectioning and staining. However, cell growth was not uniformly observed (especially in the FDA assay) and this was attributed to space limitations for growth within the microporous interior. Continued development of this process and adaptation to cells such as pancreatic islets is expected to lead to hybrid artificial organs which are capable of ameliorating metabolic disorders such as diabetes.
 ...
PMID:Microencapsulation of CHO cells in a hydroxyethyl methacrylate-methyl methacrylate copolymer. 367 22

A fast routine method has been devised to measure circulating insulin-anti-insulin complexes. The principle lies in the calculation of the difference between the insulin binding capacity of the free antibody and that of the total amount of insulin antibody. The pH of 1 aliquot of serum was lowered to 3 by adding glycine-HCl buffer. Free insulin was removed by charcoal precipitation and the pH was again neutralized by the simple addition of NaOH; the final dilution of serum was 1/5. Radiolabelled insulin was added to this and to a second aliquot of serum, also diluted 1/5. Free and bound insulin were separated using either dextran charcoal or PEG 6000 at a final dilution of 14.3%. The first technique of separation was preferred. This method has been used in normal controls and in insulin-treated diabetic patients and the results have been compared to those obtained using other methods to detect insulin-anti-insulin complexes and insulin antibodies. Insulin-anti-insulin complexes tended to be more frequently observed in patients with high insulin antibody values. The technique described is much less laborious than other methods for detecting insulin complexes since it requires only a few hours to complete. It is reproducible and sensitive enough for clinical research. This method is of value when both free and bound insulin antibodies have to be evaluated.
Diabetes Res 1986 Oct
PMID:A fluid-phase routine method for the detection of insulin-anti-insulin complexes. 381 46

Earlier investigations have revealed that polyethylene glycol-B1-insulin (PEG insulin) causes lower utilization of glucose in fat cells than does the unaltered hormone, even though the blood glucose-lowering activity of both preparations in intact animals is identical. The present study was aimed to establish whether or not PEG insulin in regard to adipose tissues of intact animals has similar functions. Radioactive glucose was used to examine the influence of both native pork insulin and its PEG derivative on the incorporation of tracers into lipids. Male Wistar rats and male domestic rabbits received 14C- and/or 3H-labeled glucose intravenously, while the insulin preparations were administered by either the subcutaneous (s.c.) or the intravenous (i.v.) route. Under the influence of PEG insulin, diminished incorporation of 14C and/or 3H into adipose tissues was observed in all cases, yet both natural insulin and the derivative lowered the blood glucose to the same extent. These observations allow the assumption that, by using certain modified insulins, it may also be possible to manipulate the extent of glucose metabolism by lipid tissues in diabetic patients.
Diabetes 1983 Oct
PMID:Influence of polyethylene glycol insulin on lipid tissues of experimental animals. 635 80

A comparative study of four nonspecific screening techniques (direct nephelometry, PEG-C4, PEG-IgG, and radiolabeled Clq binding) for immune complexes (IC) and of a technique specific for the detection of insulin-anti-insulin IC was undertaken in four groups of patients with diagnosis of infectious endocarditis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and diabetes. The highest frequency of positive results was given by the PEG-IgG test in RA, the Clq-binding test in SLE, the insulin-anti-insulin IC screening test in diabetes, and the PEG-IgG and Clq-binding tests in infectious endocarditis. Of the four nonspecific tests, the PEG-C4 assay appeared to be the least discriminative, since it failed to show significant differences between any group of patients and the group of controls. Direct nephelometry, PEG-IgG, and radiolabeled Clq binding gave consistently higher results in RA than in other diseases, and in this disease the rates of agreement between these tests were highly significant. Significant agreements between the rates of positivity of Clq binding and PEG-IgG tests were seen in all groups of patients studied. Spearman's analysis of rank showed the best correlations among tests based on similar principles (ie, PEG precipitation), and also a strong correlation between Clq binding and the PEG-IgG test in RA. The PEG-IgG test appears to be a reliable IC screening test for general use with the advantage of not involving radioisotopes. In regard to antigen-specific tests, although their specificity and sensitivity may be high, their results may show no correlation with nonspecific screening tests nor with the presence or absence of clinical or laboratory abnormalities suggestive of IC deposition, as exemplified by the insulin-anti-insulin IC screening test in diabetic patients.
 ...
PMID:Statistical analysis of five immune complex screening assays: patterns of detection in patients with rheumatoid arthritis, systemic lupus erythematosus, infectious endocarditis, and diabetes mellitus. 638 65

Treatment of diabetes mellitus by insulin injections provides long-term control of the disease but lacks any feedback response to glucose concentration changes, which finally leads to a number of life-threatening conditions. The purpose of this study was to improve and optimize an implantable, concanavalin A (Con A) based, glucose-responsive insulin delivery system studied earlier [Jeong, S. Y., Kim, S. W., Holmberg, D. L., and McRea, J. C. (1985) J. Controlled Release 2, 143-152], which can be used for long-term diabetes treatment. To optimize the "insulin component" of the delivery system, we prepared PheB1 insulin amino group monosubstituted monoglucosylpoly(ethylene glycol) (G-PEG) insulin conjugates (PEG M(r) 600 or 2000), which showed preserved bioactivity, significantly improved solubility and solution stability at neutral pH, and substantially suppressed hexamerization/dimerization. To improve the delivery system further, we synthesized and characterized a conjugate of Con A and monomethoxypoly(ethylene glycol) (mPEG, M(r) 5000) grafted hydrophilic poly(vinylpyrrolidone-co-acrylic acid) (PVPAA) with M(r) of 250,000. The optimal conjugate contained around eight PEG chains and two to three Con A tetramers attached through the amide bonds to the PVPAA chain. The Con A sugar binding characteristics were preserved, and, more importantly, Con A solubility at pH 7.4 substantially increased. This also holds true for a complex formed by the Con A conjugate and G-PEG insulin, which is soluble and does not precipitate under the physiologically relevant conditions under which the complex formed by the Con A conjugate and glycosyl insulin immediately precipitates. Finally, no leakage of the Con A conjugate from a membrane device was detected. Preliminary in vitro release experiments with Con A conjugate and G-PEG insulin complex enclosed in the membrane device showed a pulsative, reversible release pattern for G-PEG insulin in response to glucose challenges of 50-500 mg/dL, demonstrating the feasibility of the release system for use in planned, chronic in vivo studies with diabetic (pancreatectomized) dogs.
 ...
PMID:Glucose-induced release of glycosylpoly(ethylene glycol) insulin bound to a soluble conjugate of concanavalin A. 932 29


1 2 3 4 5 6 7 8 9 10 Next >>