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)

Twenty-four hour urine specimens of 67 diabetic children aged 1-17 years without any renal manifestations were examined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The excretion of high molecular weight, i.e. glomerular proteins was compared to that of low molecular weight, i.e. tubular proteins corresponding to more or less than 68,000 daltons. The glomerulo-tubular protein ratio (GTPR) obtained was significantly lower in diabetic patients compared with 30 healthy children of the same age and showed a linear decrease with longer duration of diabetes.
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PMID:Low molecular weight proteinuria in diabetic children--a marker of early diabetic nephropathy? 399 56

Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.
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PMID:Composition, removal and metabolic fate of chylomicrons derived from diabetic rats. 399 73

The presence of soluble fibrin complexes (SFC) measured by gel filtration of plasma on 4% agarose columns, fibrinogen heterogeneity on 3.5% SDS-polyacrylamide gels and the concentrations of several plasma proteins were evaluated in 39 patients with diabetes mellitus (DM) and 19 matched control subjects. A small but significant increase of SFC was found in DM (p less than 0.01). On individual basis 51.2% of the patients had increased SFC (greater than M + 2 SD of the controls). Polyacrylamide gel electrophoresis of the SFC showed no evidence of cross-linking or proteolysis. Plasma clots formed in the presence of EDTA and trasylol were analysed in SDS-polyacrylamide gels in a normal and two lower molecular weight fibrin bands (band I, II, III). The percentage of band I fibrinogen was in diabetics (65.3 +/- 4.7%) lower than that of the controls (71.8 +/- 4.5%) (p less than 0.01). Fibrinogen levels, antithrombin III, alpha 1-antitrypsin, alpha 2-macroglobulin and plasminogen were significantly increased in DM. We suggest that in DM there is an enhancement of intravascular fibrin formation and accelerated fibrinogen degradation to lower molecular weight forms.
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PMID:Soluble fibrin complexes and fibrinogen heterogeneity in diabetes mellitus. 616 8

A complex between serum albumin and immunoglobulins was observed on immunoelectrophoresis in six patients. Two patients with multiple myeloma had monoclonal IgA-albumin complexes; one of these complexes was formed by covalent bonds and the other by non-covalent bonds. Four patients displayed non-covalent IgG-albumin complexes: of these, one had multiple myeloma, two had been treated with nitrofurantoin for prolonged periods, and one had diabetes mellitus. The IgG-albumin complex of the last patient was subjected to a detailed immunochemical analysis. The albumin-specific antibodies were isolated by affinity chromatography and analysed, using a sensitive tritium labelling technique. The antibodies were polyclonal, complexed with serum albumin through their Fab portion, and showed a high specificity for the human albumin as compared with bovine and rabbit albumins. The serum albumin of two patients displayed an abnormal behaviour in reduced SDS-polyacrylamide gel electrophoresis (PAGE). The abnormal albumins had an apparent molecular weight of 52,000 and could react with rabbit anti-human serum albumin like the normal protein. No abnormal albumin could be detected in 20 other patients' sera, including nitrofurantoin-treated patients and normal controls. These findings suggest a possible role for an altered self-component in the triggering of a specific autoimmune reaction.
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PMID:Albumin-immunoglobulin complexes in human serum: classification and immunochemical analysis. 617 76

Islet cell surface antibodies (ICSA) have been generated to investigate relations between recognition of specific antigens and cytotoxic reactions on pancreatic islet cells. Sera from rabbits which had been directly immunized with islet cells or intact rat islets exhibited positive immunofluorescence with both rat and rabbit pancreatic islet cells. Analysis by SDS polyacrylamide gel electrophoresis and autoradiography of islet cells proteins prelabeled with [35S]methionine revealed that these sera precipitated a specific protein of Mr 40000. Serum from immunized rabbits stimulated 51Cr-release in suspensions of dispersed islet cells prepared from neonatal rats. Absorption to lymphocytes and liver powder removed antibodies that were cytotoxic to lymphocytes but complement-mediated cytotoxicity against islet cells persisted. Circulating ICSA neither in rabbits nor in rats caused changes in blood glucose. Moreover, no major alterations of islet cells in the immunized rabbits were observed upon electron microscopic examination. It is concluded that ICSA are capable of recognizing specific islet cell antigens and thus mediate complement-dependent cytotoxic reactions in vitro, but the mere presence of ICSA is obviously not sufficient to induce diabetes in vivo under the conditions used.
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PMID:Absence of cytotoxicity of islet cell surface antibodies in vivo despite complement-mediated cytotoxic effects to islet cells in vitro. 620 50

Insulin aggregation remains a fundamental obstacle to the long-term application of many insulin infusion systems. We here report the effects of physiologic and nonphysiologic compounds on the aggregation behavior of crystalline zinc insulin (CZI) solutions. Under conditions chosen to simulate the most severe that would be encountered in delivery systems (presence of air, continuous motion, and elevated temperature), both highly purified and regular CZI at 5 U/ml formed turbid gels in 5 days. At concentrations of 100 and 500 U/ml stability was increased with turbid gels forming at 12 and 15 days, respectively. Under identical conditions, 5 U/ml CZI formulations containing the physiologic surfactant lysophosphatidylcholine (0.02%) or the synthetic surfactants SDS (1%), Brij 35 (0.1%), Tween (0.01%), or Triton X (0.01%) retained a transmittance at 540 nm of greater than 96% for 67-150 days. These nonionic and ionic surfactants containing the hydrophobic group, CH3(CH2)N, with N = 7-16, remarkably stabilized CZI formulations while those lacking such groups demonstrated little or no effect. The alcohols glycerol (30-50%) and isopropanol (10-50%) were moderately effective stabilizers. Silicone rubber drastically accelerated aggregation in all but one formulation (1% SDS). Emphasis in this study was placed on the properties of 5-U/ml formulations. Controls run at higher concentrations indicated a positive correlation between concentration and stability. It was concluded that the aggregation of insulin into high-molecular-weight polymers may be inhibited by reducing the effective polarity of the solvent. In this regard, anionic and nonionic surfactants containing appropriately long hydrophobic groups demonstrated the greatest degree of stabilization. Finally, of all the medical grade materials likely to be used in pumps, silicone rubber is the most active in promoting insulin aggregation.
Diabetes 1983 May
PMID:Physical stability of insulin formulations. 634 Nov 25

Insulin receptors on viable rat adipocytes were affinity-labeled using a biologically active and photosensitive analogue of insulin, 125I-B2(2-nitro, 4 azidophenylacetyl)-des-PheB1-insulin (125I-NAPA-DP-insulin). The radiolabeled proteins were identified by SDS polyacrylamide gel electrophoresis and autoradiography. Binding of 125I-NAPA-DP-insulin (40 ng/ml) to rat adipocytes at 16 degrees C, followed by photolysis, resulted in the specific labeling of essentially one protein with an apparent molecular weight of 430-450,000 daltons. When this radiolabeled protein was treated with dithiothreitol prior to electrophoresis, specific labeling occurred predominantly in a 125,000-dalton protein and to a lesser extent in a 90,000-dalton protein. In addition, there was a minimal amount of specific labeling of a 115,000-dalton protein. Under certain experimental conditions, the nonreduced form of the photoaffinity-labeled receptor appeared as a heterogeneous population of proteins having apparent molecular weights of 430,000, 350,000, and 270,000 daltons. Subsequent to photoaffinity labeling of insulin receptors at 16 degrees C, adipocytes were incubated at 37 degrees C for various periods of time to allow for internalization. This resulted in an initial rapid loss of radioactivity in the 430,000- and 125,000-dalton bands. At 60 min the amount of radioactivity in each of these bands was approximately 50% of that present before incubation at 37 degrees C and stayed constant for 120 min. A first-order plot of the decline in receptor-associated radioactivity was biphasic with the initial phase having a half-life of 1.4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 Nov
PMID:Degradation of insulin receptors in rat adipocytes. 635

Insulin binding and processing was studied in monolayer cultures of bovine aortic endothelial cells. Specific 125I-insulin binding was both time and temperature dependent. Maximum binding at 37 degrees C occurred at 90 min, and was 3.8%/mg protein and, at 15 degrees C, 7%/mg protein at 4 h. 125I-insulin was crosslinked to its receptor using disuccinimidyl suberate (DSS), and the structure of the receptor complex was identified by SDS-polyacrylamide gel electrophoresis and autoradiography; a major band with Mr = 145,000 was identified, which corresponds to the alpha-subunit of the insulin receptor reported in other tissues. Receptor-bound insulin was internalized, and both the rate and the amount of internalization were temperature dependent. The rate of internalization was slowest at 4 degrees C, and fastest at 37 degrees C, and the maximum amount of 125I-insulin internalized in 120 min was 16% at 4 degrees C, 45% at 15 degrees C, and 81% at 37 degrees C. Despite the high rate of internalization, endothelial cells do not appear to degrade insulin significantly, as determined by gel chromatography and TCA solubility (7% at 4 h) of media-associated radioactivity. In addition, the majority of internalized insulin (75%) was released by 60 min, largely as intact insulin. Chloroquine treatment at high concentration did not exert any major effect on insulin binding or degradation within the first 60 min, but thereafter produced a marked increase in cell-associated radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Aug
PMID:Processing of insulin by bovine endothelial cells in culture. Internalization without degradation. 637 2

The effects of insulin and insulin-like growth factor I (IFG-I) on protein synthesis were compared in muscle isolated from lean and goldthioglucose (GTG)-obese mice. Two types of skeletal muscles, the red soleus and the white extensor digitorum longus (EDL) muscles, were studied. In muscles from lean mice, 6.7 nM insulin and 50 nM IGF-I caused a similar maximal stimulation of tyrosine incorporation in total proteins (40% increase). However, the potency of IGF-I was only 5-10% that of insulin both in soleus and in EDL muscles (EC50 approximately equal to 6 nM for IGF-I and 0.5 nM for insulin). Basal rate of protein synthesis was identical in muscles from GTG-obese and lean mice. Similarly, a comparable increase in the rate of protein synthesis was obtained using maximally effective concentrations of insulin and IGF-I in both lean and GTG-obese animals. SDS-polyacrylamide gel electrophoresis analysis of proteins labeled with 35S-methionine confirmed that, in muscles from lean and GTG-obese animals, insulin and IGF-I increased overall protein synthesis in a similar manner. These results suggest that the protein synthesis machinery is not impaired in GTG-induced obesity, which is therefore not associated with resistance to insulin for its effect on protein metabolism.
Diabetes 1983 May
PMID:Insulin and insulin-like growth factor I. Effects on protein synthesis in isolated muscles from lean and goldthioglucose-obese mice. 640 79

The amount of nonenzymatic glycosylation present in normal and diabetic rat peripheral nerve myelin, whole brain, brain myelin, and individual myelin protein components was determined using NaB3H4 reduction followed by either boronic acid affinity chromatography or SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Diabetic peripheral nerve myelin (PNS-M) showed a 5.2-fold increase over normal, indicating that myelin is the major peripheral nerve component undergoing excessive glycosylation in diabetes. SDS-PAGE of diabetic and normal PNS-M showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. However, in the diabetic, the amount of incorporated radioactivity was 3.74 times greater in the P0 protein and 2.8 times greater in the high-molecular-weight material that did not enter the gel. In whole brain, a 2.4-fold increase in the amount of nonenzymatic glycosylation was observed when diabetic was compared with normal, while diabetic brain myelin (CNS-M) was 3.8 times more glycosylated than normal brain myelin. SDS-PAGE of diabetic and normal CNS-M, like that of PNS-M, showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. The amount of incorporated radioactivity, however, was 3.18 times greater in the proteolipid region, 2.37 times greater for basic myelin protein, and 2.9 times greater for the high-molecular-weight proteins that did not enter the gel. This excessive nonenzymatic glycosylation of the main peripheral and central nervous system myelin components may contribute to the functional abnormalities of myelinated neurons associated with diabetes.
Diabetes 1983 Jul
PMID:Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. 686 12


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