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)

The hepatic asialoglycoprotein receptor is the first studied mammalian lectin. Modulations in vivo by diabetes and in vitro by the carboxylic ionophore monensin gave rise to similar apparent alterations on its biosynthesis, structure and ligand binding capacity. In normal rats, the receptor (whether purified by ligand or antibody-affinity chromatography) presented a similar pattern in SDS-PAGE analysis, with a major 42-kDa band and two minor ones (49 and 52-54 kDa). In diabetic rats, a new 38-kDa band appeared, but only after antibody-affinity purification. In vitro biosynthesis of the receptor by normal hepatocytes in the presence of 35S-methionine showed that this 38-kDa band was present at the end of a 30-min pulse but decreased during a 180-min chase, in association with an increase in the major 42-kDa band. In diabetic cells, this evolution was retarded. Using a 30-min pulse followed by a 120-min chase in the presence of 100 microM monensin, we showed that this carboxylic ionophore had similar effects on diabetes, leading to a delay in the maturation process of the 42-kDa band and the persistent emergence of the 38-kDa species. Allowing incubation in the presence of 25 or 100 microM monensin, we observed a decrease in the number of ligand binding sites both at the surface (40%) and within the cell (28%). In hepatocytes from diabetic rats, monensin showed no additional effect on the partial diabetes-induced inactivation.
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PMID:Comparative effects of diabetes and monensin on the lectin asialoglycoprotein receptor: biosynthesis, structure and function in rats. 157 3

Advanced glycosylation endproducts (AGEs), the glucose-derived adducts that form nonenzymatically and accumulate on tissue proteins, are implicated in many chronic complications associated with diabetes and aging. We have previously described a monocyte/macrophage surface receptor system thought to coordinate AGE protein removal and tissue remodeling, and purified a corresponding 90-kD AGE-binding protein from the murine RAW 264.7 cell line. To identify AGE-binding proteins in normal animals, the tissue distribution of 125I-AGE rat serum albumin taken up from the blood was determined in rats in vivo. These uptake studies demonstrated that the liver was a major site of AGE protein sequestration. Using a solid-phase assay system involving the immobilization of solubilized membrane proteins onto nitrocellulose to monitor binding activity, and several purification steps including affinity chromatography over an AGE bovine serum albumin matrix, two rat liver membrane proteins were isolated that specifically bound AGEs, one migrating at 60 kD (p60) and the other at 90 kD (p90) on SDS-PAGE. NH2-terminal sequence analysis revealed no significant homology between these two proteins nor to any molecules available in sequence databases. Flow cytometric analyses using avian antibodies to purified rat p60 and p90 demonstrated that both proteins are present on rat monocytes and macrophages. Competition studies revealed no crossreactivity between the two antisera; anti-p60 and anti-p90 antisera prevented AGE-protein binding to rat macrophages when added alone or in combination. These results indicate that rat liver contains at least two novel and distinct proteins that recognize AGE-modified macromolecules, although p90 may be related to the previously described 90-kD AGE receptor isolated from RAW 264.7 cells. The constitutive expression of AGE-binding proteins on rat monocytes and macrophages, and the sequestration of circulating AGE-modified proteins by the liver, provides further evidence in support of a role for these molecules in the normal removal of proteins marked as senescent by accumulated glucose-derived covalent addition products, or AGEs.
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PMID:Two novel rat liver membrane proteins that bind advanced glycosylation endproducts: relationship to macrophage receptor for glucose-modified proteins. 165 76

Na+/K(+)-ATPase was evaluated in the retina and kidney of the spontaneously diabetic BB/Wor rat after 1 and 4 months of insulin dependency. Retinal synthesis of the Na+/K(+)-ATPase was measured during a 2-h intravitreal pulse of [35S]methionine and analyzed by SDS-PAGE and scintillation counting. Synthesis of the alpha-1 and 'alpha(+)' (includes both alpha-2 and alpha-3) isoforms of the catalytic subunit was increased 123% and 69%, respectively at 4 months. Increases were also suggested at 1 month, but were not significant. The diabetes-dependent peak of synthesis in long-term diabetic rats turned over rapidly and by 3 days after intravitreal labeling, radioactively labeled enzyme was equal in both control and diabetic retinae. The amount of axonally transported, labeled enzyme recovered from endings of the optic nerve in the superior colliculus paralleled retinal labeling. Significant renal hypertrophy (48%) was noted at 4 months, but not at 1 month. The strophanthidin-inhibition constant for diabetes-induced renal enzyme was the same as for control enzyme (approx. 10(-4) M), indicating that diabetic renal hypertrophy does not induce a Na pump isozyme that is more sensitive to cardiotonic steroids. SDS-PAGE of the renal enzyme also failed to indicate more than one isoform of the alpha subunit.
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PMID:Molecular isoforms of Na+/K(+)-ATPase in the nervous system and kidney of the spontaneously diabetic BB/Wor rat. 166 41

The metabolism of glutathione and activities of its related enzymes were investigated in erythrocytes from patients with diabetes mellitus. A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were observed in erythrocytes from diabetics whose fasting plasma glucose was more than 140 mg/dl. The activity of glutathione reductase decreased in diabetics, while that of glutathione peroxidase did no change. ATP-depended outward transport of glutathione disulfide also decreased in diabetics. These data suggest that the increase in the levels of glutathione disulfide in erythrocyte from diabetics is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. Glycated gamma-glutamylcysteine synthetase determined using a boronate affinity column chromatography was higher in diabetics than in normal controls. The rate of glutathione synthesis using (H3)-glycine decreased in diabetics. The decrease is the levels of reduced form of glutathione is erythrocytes of diabetics is thought to be brought about by impaired glutathione synthesis. In order to study the mechanism by which glutathione synthesis is impaired, gamma-glutamylcysteine synthetase was purified from human erythrocytes. The molecular weight of the purified enzyme was 60K. A single band was observed on SDS polyacrylamide gel electrophoresis. When the purified enzyme was incubated with glucose, the enzyme activity decreased dependent on the incubation time. These data suggest that the impaired glutathione synthesis in diabetics is brought by glycation of gamma-glutamylcysteine synthetase. As conclusion, glutathione metabolism is impaired in erythrocytes from diabetics which weaken the defence mechanism against oxidative stress in these patients.
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PMID:[Glutathione metabolism in erythrocytes from patients with diabetes mellitus]. 167 80

Both insulin and glucocorticosteroid (GS) deficiency causes a reduction of amylase synthesis and changes in the dose-response curve of cholecystokinin (CCK) stimulated enzyme secretion in rats. Since we found a reduction of plasma insulin in adrenalectomized rats, we now tested the hypothesis that the regulation of amylase synthesis by insulin may be mediated by GS. Three groups of male rats were investigated: controls, streptozotocin induced diabetics, and diabetics treated with GS. Animals were sacrificed 10-14 days after injection of streptozotocin and isolated pancreatic acini prepared by collagenase digestion. Protein synthesis was measured on the translational level by incubation of acini with 35S-methionine followed by lysis of cells and separation of proteins by SDS-PAGE. In addition, protein synthesis was measured on the transcriptional level by isolation of mRNA from pancreatic acini and translation of proteins using the rabbit reticulocyte lysate system. The loss of insulin in diabetic rats was associated with a 70-90% decrease in amylase synthesis and increases of synthesis of various proteases. This was due to a specific decrease in mRNA coding for amylase and increase in mRNA coding for proteases. Furthermore, the known rightward shift of the dose response curves of CCK stimulated amylase secretion was seen in diabetic animals. Treatment of diabetic rats with GS did deteriorate the catabolic status seen in diabetes with increases in mortality as compared to diabetes alone. However, neither the overall pattern of enzyme synthesis seen in diabetic rats nor the alterations in CCK stimulated enzyme secretion were changed by treatment with GS. We conclude that the regulation of amylase synthesis and enzyme secretion by insulin is not mediated via GS.
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PMID:Pancreatic enzyme synthesis and secretion are independently regulated by insulin and glucocorticosteroids. 170 71

Testicular blood vessels contain IGF-I and IGF-II/M6P receptors. Binding to these receptors was altered following treatment with streptozotocin to induce diabetes. Intensity of labelling and size of receptors were examined using SDS-gel electrophoresis and autoradiography. The IGF-I and IGF-II/M6P receptor of the diabetic rat testicular microvessels appear to have a lower molecular weight as compared to controls. Macro- and microvascular tissues from diabetic rats apparently contain more IGF-I receptors than normal Sprague-Dawley rats. Using immunohistochemical techniques, the IGF-II/M6P receptor appears to dissociate easier from diabetic rat testicular arteries than from control animal blood vessels. M6P appears to increase both IGF-I and IGF-II binding to the rat IGF-II/M6P receptor, at least as visualized using affinity crosslinking analysis. Whether these differences in the IGF receptors are involved in the development of diabetic vascular disease is not yet known.
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PMID:Insulin-like growth factor receptors in testicular vascular tissue from normal and diabetic rats. 172 19

Patients with type II diabetes mellitus were assessed for symptoms of depression using the Zung Self-Rated Depression Scale (Zung SDS) and the Beck Depression Inventory (BDI). The patients were classified according to the presence or absence of diabetic complications, and they were compared with a group of demographically matched, nonmedically ill control subjects. The patients with diabetic complications scored significantly higher on the depression inventories than did the patients without complications and the control subjects. Factor analysis of BDI responses revealed that cognitive symptoms of depression were prominent in the diabetic patients with complications. In this group, 74% of patients scored within the range of clinical depression on the BDI; 35% scored within the range of severe depression. Symptoms of sexual dysfunction were significantly correlated with symptoms of depression in diabetic women but not in diabetic men. The findings are discussed within the context of other research in the behavioral aspects of diabetes mellitus.
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PMID:Symptoms of depression in patients with type II diabetes mellitus. 188 19

Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from the circulation with a T1/2 alpha of 2.9 min and a T1/2 beta of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated that 125I-rIL-1 beta was localized to the proximal tubules in the kidney and to the hepatocytes in the liver. Furthermore, grains were localized to the islets of Langerhans in the pancreas. Tracer-bound proteins corresponding to intact 125I-rIL-1 beta were found in the circulation after i.v., intraperitoneal (i.p.) and subcutaneous (s.c.) injections, as demonstrated by high performance size exclusion chromatography, trichloracetic acid precipitation and SDS-PAGE until 5 h after tracer injection. Pre-treatment with 'cold' rIL-1 beta enhanced degradation of a subsequent injection of tracer. The route of administration was of importance for the biological effects of rIL-1 beta, as demonstrated by a reduced food intake, increased rectal temperature and blood glucose after s.c. injection of rIL-1 beta compared with i.p. The present demonstration of intact rIL-1 beta in the circulation and the islets of Langerhans supports the hypothesis that systemic IL-1 beta may be involved in the initial beta-cell destruction leading to IDDM in humans.
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PMID:The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats. 194 95

In this study we demonstrate that haptoglobin, a serum glycoprotein secreted by the liver, has altered structure in the BB/Wor diabetic rat. SDS-PAGE of haptoglobin (a tetramer composed of two glycosylated beta-chains each containing two sites for Asn-linked oligosaccharides connected by disulfide bonds with two nonglycosylated alpha-chains) clearly shows that the beta-chain of haptoglobin from diabetic rats is smaller than normal, with a molecular mass of 39 instead of 40 kDa. Both acute and chronic diabetic rats exhibit the defect. Defective haptoglobin appears in the serum within 4 days of onset of the disease, but insulin therapy prevents the defect. Removal of Asn-linked oligosaccharides with peptide: N-glycosidase F from Flavobacterium meningosepticum abolished the size difference between the beta-chains from normal and diabetic haptoglobin, with the molecular mass in both cases shifting to 30 kDa. Haptoglobin from both normal and diabetic rats was resistant to digestion by endoglycosidase H from Streptomyces griseus, which cleaves high mannose-type chains. Removal of sialic acid with neuraminidase treatment resulted in a reduction in the molecular mass in both cases, but without eliminating the size difference between the two. These results demonstrate that haptoglobin from diabetic BB/Wor rats contains a structural abnormality which correlates with onset of the disease. The defect is most likely due to an alteration in Asn-linked oligosaccharides, probably involving a change in the neutral sugars of complex-type oligosaccharide chains. This finding represents the first example of an altered Asn-linked oligosaccharides in diabetes.
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PMID:Diabetic BB/Wor rat haptoglobin exhibits a probable structural abnormality in Asn-linked oligosaccharides. 202 25

An enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against surface components of rat islet and spleen lymphocytes. Live islet tumor RIN5 AH cells expressing characteristic ganglioside target antigens or rat spleen cells were immobilized onto wells of microtiter polystyrene plates precoated with poly-l-lysine and then incubated with test or normal rat sera. Cell surface-bound antibodies were quantitated after reaction with horseradish peroxidase-conjugated rabbit anti-rat Ig. With this assay, 46% (6/13) of sera from diabetes-prone BB rats and 100% (8/8) of sera from rats treated with complete Freund's adjuvant/streptozotocin (CFA/STZ) prior to immunization with RIN cells had islet cell surface antibodies: 54% (7/13) and 75% (6/8), respectively, were positive for lymphocyte antibodies (defined as the HRP anti-rat Ig binding exceeding the mean + 2SD of control group values). SDS polyacrylamide gel electrophoresis followed by immunoblotting analysis suggested that the islet cell antibodies in sera from the BB and CFA/STZ rats recognized RIN-cell components that were different in their molecular weights. These antigens were not detectable on spleen cells indicating that the ELISA described can be used to quantitate levels of islet cell specific antibodies which possibly reflect beta cell damage with progression to islet degeneration in the rat.
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PMID:Detection of antibodies to islet cell and splenic lymphocytes in diabetes-prone BB and adjuvant-streptozotocin treated Lewis rats by ELISA and immunoblot analysis. 209


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