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)

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

B-cells have previously been shown to be very susceptible to damage induced by superoxide radicals, and protection against such damage has been achieved both in vitro and in vivo with superoxide dismutase. During maturation, db/db mice develop diabetes and accumulation of potentially superoxide radical-producing leucocytes can be demonstrated in the islets during the process. To test for the possibility that superoxide radical-induced damage contributes to the development of diabetes, db/db mice were given daily ip injections of 200 mg/kg polyethylene glycol-substituted CuZn superoxide dismutase. No effect of the treatment could be demonstrated.
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PMID:No effect of superoxide dismutase on spontaneous development of diabetes in db/db mice. 328 95

The liposome technique is widely used to transport substances that cannot normally traverse the plasma membrane into the cell. The interactions of liposomes with the plasma membrane of pancreatic islet cells have not previously been studied. We evaluate the suitability of the liposome technique for introducing substances into the pancreatic beta-cell to which the cell membrane is impermeable. Liposomes were synthesized with an ether-injection method, and the cell-liposomal interactions were investigated by means of radioactive labeling and the fluorescent aqueous space marker 6-carboxyfluorescein. Experiments were performed on freshly isolated mouse pancreatic islets and on free islet cell preparations. With fluorescence microscopy, liposomes were observed to fuse spontaneously with islet cells, and the corresponding internalized volumes were quantified with spectrofluorometric measurements. The liposome association with islets and islet cell suspensions, as assessed by radioactive labeling, was found to increase with the liposome concentration. The effects of liposome membrane lipid composition on the fusion rate were found to be decreased in the presence of glucolipid. In addition, polyethylene glycol failed to affect the liposomal uptake. Freshly isolated islets incubated with liposomes containing glucose 6-phosphate were observed to release slightly more insulin than islets incubated with "empty" liposomes. In conclusion, liposomes fuse spontaneously with islet cells in vitro, and the uptake of liposomes is regulated by the lipid composition of the liposomal bilayer and the amount of liposomes present. The function of the beta-cell can be altered with the liposome technique, e.g., by addition of biologically active molecules such as glucose 6-phosphate.
Diabetes 1988 Aug
PMID:Use of liposomes to introduce substances into pancreatic islet cells. 329 31

The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6-12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p less than 0.05) mean serum C4 levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.
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PMID:Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in type 1 (insulin-dependent) diabetic children. 332 22

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

Free insulin (FI) measurements obtained by polyethylene glycol (PEG) precipitation within 3 min of drawing the blood sample (FI3) from four insulin-treated diabetic subjects with a wide range of insulin antibodies were compared with published methods of FI estimation. Comparison of FI values obtained by PEG precipitation in assays of replicate samples of the same specimens (N = 9) stored at 4 degrees C for 24 h (EFI) and FI3 were 4.76 +/- 1.5 microU/ml (mean +/- SEM) and 17.13 +/- 4.7 microU/ml, respectively (P less than 0.005). Comparison of FI values obtained in six groups of replicate samples (N = 12, 18 per group, a total of 91 specimens) from these four patients assayed immediately after thawing to 18 degrees C, and incubated at 37 degrees C for 30, 60, and 120 min, and FI3 showed a significant difference in at least one of these four comparisons (mean +/- SEM) in each of these six sample groups. In 18 of 24 comparisons there was a loss of FI when stored samples were used with or without incubation (12 of these were significant at the P less than 0.05-0.001 level), but in 6 of the 24 comparisons there was an increase in the FI against FI3 (3 of these 6 significant at the P less than 0.05-0.01 level). There was a trend toward a greater loss of FI in stored samples with higher FI3 content. Loss of FI during incubation occurred in all groups irrespective of the FI3 content.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Mar
PMID:The effect of immediate polyethylene glycol precipitation on free insulin measurements in diabetic patients with insulin antibodies. 351 36

In 60 diabetes mellitus patients the circulating immune complexes revealed during sedimentation with polyethylene glycol, were compared with the insulin binding capacity and the levels of free and total insulin. The circulating immune complexes were detected in 15 patients, the frequency of the immune complexes in type I and II diabetes mellitus being the same. The serum insulin binding capacity, the level of total insulin and the ration of total and free insulin were much higher in the patients on a long-term insulin therapy than in those who started to receive insulin and in untreated patents. The insulin binding capacity and the insulin nonspecific binding reflecting the level of antibodies to insulin, did not correlate with the level of the immune complexes. However in type I diabetes mellitus patients the level of bound insulin showed good correlation with the level of the circulating immune complexes. The circulating immune complexes revealed during sedimentation with polyethylene glycol, reflected, in particular, insulin binding to antibodies.
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PMID:[Circulating immune complexes and insulin-binding capacity of the serum of diabetics]. 352 May 40

There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of Mr 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation of IgM from IgG to prevent interference between the two antibody classes. Plasma samples from 10 newly diagnosed IDDM children and 10 healthy controls were precipitated with polyethylene glycol (PEG), and the crude Ig was subjected to Sephacryl S-300 chromatography to separate IgM and IgG. ICA determined by indirect immunofluorescence on frozen sections of human pancreas showed reduced background immunofluorescence intensity in the purified fractions compared with crude plasma. The number of ICA-positive samples among the IDDM patients increased from 7/10 in plasma to 9/10 in the IgG fraction. There was an increase in the ICA titer in 6/9 of the positive samples. All purified IgM samples were ICA negative. Immunoprecipitation experiments by using Nonidet P-40 detergent lysates of [35S]methionine-labeled neonatal rat islets demonstrated that the 64,000 autoantibodies were in the IgG fraction. We found 7/10 IDDM samples to be positive, whereas all controls were negative. The background in the autoradiographic analysis was markedly reduced in the IgG fractions compared with immunoprecipitates with crude or PEG-purified plasma and the IgM fraction. ICA titers did not correlate to the ability of the IgG fraction to precipitate the 64,000 autoantigen. It is concluded that both the ICA and 64,000 autoantibodies are primarily of the IgG class at the time of clinical onset of IDDM, and that purification of IgG from human IDDM plasma facilitates the detection of the rat islet cell 64,000 antigen.
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PMID:Islet cell and 64K autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children. 353 24

A new, simple insulin-receptor-binding assay has been devised. The assay is based on the separation of free and receptor-bound 125I-labeled insulin in 80% ethanol. It was found that the insulin-receptor complex was fully stable at this ethanol concentration, regardless of the source of the receptor employed. The assay has been evaluated with solubilized insulin receptors and membrane-bound receptors from human placenta and porcine liver as well as intact cells with the IM-9 cell line. The assay is simple, rapid, and has large capacity. Comparisons of the ethanol-based assay to the conventionally employed assays with polyethylene glycol or microfuge centrifugation for the separation of free and bound 125I-insulin revealed large discrepancies between the assays. The ethanol-based assay always appeared to provide a better separation. Microfuge centrifugation of placental membranes precipitated approximately 3% of the ethanol-precipitable insulin-receptor complex, while polyethylene glycol precipitation of solubilized insulin receptors varied between 40 and 80% of the ethanol precipitability, depending on the receptor concentration employed.
Diabetes 1987 Mar
PMID:New, simple insulin-receptor assay with universal application to solubilized insulin receptors and receptors in broken and intact cells. 354 55

Blood sampling on filter paper was tested for determination of glycated haemoglobin. The method showed coefficients of variation of 3.4% and 4.1%, and linearity coefficients of 0.978 and 0.91 for the microchromatographic and colorimetric methods respectively. A blood sample on filter paper impregnated with 5% ethylene glycol solution remains stable for 8 days at room temperature. In a group of 30 diabetics educated in the filter paper blood sampling technique, no statistically significant differences were registered among the mean values of their blood glucose profiles, glycated haemoglobin levels determined at the hospital and those obtained at home 14 days after discharge. In conclusion, the use of blood spotted on filter paper seems a cheap and convenient method for collecting, storing and transporting samples for analysis of glycated haemoglobins. It is also a useful alternative for home monitoring of diabetics. Moreover, it could also be useful in epidemiological studies of diabetes.
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PMID:Filter paper blood sampling for glycated haemoglobin determination and its use in the control of diabetes mellitus. 362 29


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