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)

N epsilon-(carboxymethyl)lysine, N epsilon-(carboxymethyl)hydroxylysine, and the fluorescent cross-link pentosidine are formed by sequential glycation and oxidation reactions between reducing sugars and proteins. These compounds, termed glycoxidation products, accumulate in tissue collagen with age and at an accelerated rate in diabetes. Although glycoxidation products are present in only trace concentrations, even in diabetic collagen, studies on glycation and oxidation of model proteins in vitro suggest that these products are biomarkers of more extensive underlying glycative and oxidative damage to the protein. Possible sources of oxidative stress and damage to proteins in diabetes include free radicals generated by autoxidation reactions of sugars and sugar adducts to protein and by autoxidation of unsaturated lipids in plasma and membrane proteins. The oxidative stress may be amplified by a continuing cycle of metabolic stress, tissue damage, and cell death, leading to increased free radical production and compromised free radical inhibitory and scavenger systems, which further exacerbate the oxidative stress. Structural characterization of the cross-links and other products accumulating in collagen in diabetes is needed to gain a better understanding of the relationship between oxidative stress and the development of complications in diabetes. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.
Diabetes 1991 Apr
PMID:Role of oxidative stress in development of complications in diabetes. 201 41

Allogeneic islets obtained from Lewis rats were transplanted into diabetic BB/W rats with or without cyclosporine. In addition, these islets were encapsulated in alginate-poly L-lysine membranes and then transplanted into diabetic BB/W rats with or without immunosuppressive and/or antiinflammatory agents. The agents used were cyclosporine, dexamethasone, indomethacin (Ind), or a combination of these. Our results show that islets alone survived for 7 days, with or without CsA therapy. Encapsulated islets survived for 14.2 days, and this was extended by CsA, Dex, or CsA + Ind. Loss of encapsulated graft functions was associated with formation of a dense pericapsular infiltrate, which was inhibited by CsA, Dex, CsA + Ind, or CsA + Dex. In addition, the infiltrate was reduced in animals that had diabetes for long periods of time (greater than 5 months versus less than 1 month). Empty capsules also provoked this cellular response. Thus, encapsulation of islets resulted in slightly prolonged islet survival, which was further enhanced by immunosuppression.
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PMID:Transplantation of encapsulated allogeneic islets into diabetic BB/W rats. Effects of immunosuppression. 201 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

The anticancer activity of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine (CNC-omega-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-omega-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-omega-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (less than 20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.
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PMID:Antineoplastic efficacy of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine, in combination with diazoxide or insulin in autochthonous mammary carcinoma of the Sprague-Dawley rat. 210 82

The localization of glycated protein in the kidney of diabetic rats was examined immunohistochemically with antiserum against glucitol-lysine. In diabetic rats the brush border and basement membrane of the proximal convoluted tubules were strongly immunoreactive with the antiserum but in control rats, only the brush border was weakly reactive. The immunoreactive tubules were more abundant in diabetic rats. No immunoreaction was found in any other structures in the kidney. Glycation of the proximal convoluted tubules may be an alteration in diabetic nephropathy.
Diabetes Res Clin Pract 1990 Mar
PMID:Immunohistochemical localization of glycated protein in diabetic rat kidney. 211 Dec 38

Islets of Langerhans were isolated from WAGola rats and encapsulated in high mannuronic acid sodium alginate droplets. The capsules were completed in the following ways: (a) poly-l-lysine alone, (b) poly-l-lysine plus high guluronic acid alginate, (c) poly-l-lysine plus high mannuronic acid alginate. Islet viability was assessed every 3-4 days over a period of 4 weeks, by a microfluorometric assay using fluorescein diacetate and propidium iodide, and every 7 days by perifusion. The perifusion results were corrected for DNA content to take islet size differences into account. The results from the microfluorometric assay showed a generally high viability of the islets in all groups at each time interval. The perifusion experiments showed that the response time and stimulation indices of the islets was similar in all groups, but the absolute amount of insulin released was slightly lower from encapsulated islets relative to unencapsulated controls. It was concluded that the presence of a capsule, regardless of its composition, did not adversely affect the membrane integrity of the islets, their response time, nor their proportionate increase in insulin release following glucose stimulation. However, the absolute amount of insulin released from encapsulated islets was reduced during perifusion. This reduction was apparent after 1 week in culture, but remained stable thereafter.
Diabetes Res 1990 Jul
PMID:A study of the effect of capsule composition on the viability of cultured alginate/poly-l-lysine--encapsulated rat islets. 213 84

Reovirus type 2 that had been isolated from a cow with diarrhoea and passaged in bovine kidney cell culture produced a Type 1 (insulin-dependent) diabetes-like syndrome when inoculated into NC mice. The infection resulted in insulitis and destruction of islet cells. Viral antigens were found in islet cells by staining with fluorescein-labelled antibody to reovirus type 2. The destruction of islet cells resulted in abnormalities shown on glucose tolerance testing. Studies on the susceptibility of the host showed that only certain strains of mice had overtly abnormal glucose tolerance tests when infected with reovirus type 2. To assess the immunological role in the pathogenesis of reovirus type 2-induced diabetes, infected mice were subjected to immunosuppressive or thymic hormone treatment. The administration of either anti-thymocyte serum or serum thymic factor reduced or prevented the development of the diabetes-like syndrome, while Arg-Lys-Asp-Val-Try did not show any therapeutic effects.
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PMID:Reovirus type 2-induced diabetes in mice prevented by immunosuppression and thymic hormone. 216 69

Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Because high-density lipoprotein (HDL) is believed to protect against atherosclerosis and is glycosylated at increased levels in diabetic individuals, the effects of nonenzymatic glycosylation of HDL3 on binding of HDL3 to cultured fibroblasts and to the candidate HDL-receptor protein were examined. HDL3 was glycosylated in vitro with glucose alone or in combination with sodium cyanoborohydride. With this catalyst, up to 40-50% of the lysine residues could be glycosylated, resulting in a progressive drop to nearly 60% in high-affinity binding to cultured fibroblasts at 4 degrees C. Binding to the 110,000-Mr candidate HDL-receptor protein was reduced by almost 75%. At levels of HDL glycosylation equivalent to the 3-5% observed in diabetes, high-affinity binding to fibroblasts at 4 degrees C was diminished by up to 15-20%. Binding kinetic studies paradoxically suggested that glycosylated HDL3 binds with higher affinity to a reduced number of binding sites. The findings in this study suggest that nonenzymatically glycosylated HDL may be functionally abnormal and might contribute to the development of atherosclerosis in patients with diabetes mellitus.
Diabetes 1990 Oct
PMID:Nonenzymatic glycosylation of HDL resulting in inhibition of high-affinity binding to cultured human fibroblasts. 217 Feb 16

We evaluated six patients in whom a diagnosis of Sheehan's syndrome had been made. The plasma levels of the following hormones were measured: basal thyroxine (T4), estradiol and cortisol; and also follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), thyrotropin (TSH), prolactin (PRL) and adrenocorticotropic hormone (ACTH), basally and after acute challenge with LH releasing hormone (LHRH), GRF (1-29)NH2 or insulin hypoglycemia, TSH releasing hormone (TRH) and lysine-8-vasopressin, respectively. Two patients underwent chronic LHRH stimulation by pulsatile subcutaneous administration with infusion pump. In 4 cases, computed tomography (CT) was performed although cranial X-ray study was normal. A severe and generalized pituitary involvement was found in all patients, 3 of whom had diabetes mellitus. Probably, more insidious cases go unnoticed. The presence of asymptomatic partial empty sella (ES) in all the CTs that were carried out raises the possibility that it is another evolutive feature of SS.
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PMID:[Relations between Sheehan's syndrome and empty sella turcica. A functional study apropos of 6 cases]. 217 69

Superoxide dismutases (SOD) and their changes in diabetes, aging, ischemia and cancer were studied, Cu, Zn-SOD undergoes glycation reaction in vitro and in vivo and loses its activity by formation of Amadori compounds. Two lysine residues of Cu, Zn-SOD, Lys-122 and Lys-128 are primary glycated sites which are located on the surface of the molecule. The sites are also located on the active site liganding loop which plays a major role in the activity. The glycated Cu, Zn-SOD increased in the red cells of diabetic patients, especially those with diabetic complications. Mn-SOD appears in the serum of patients with acute myocardial infarction in a biphasic manner. The enzyme appears in sera 16 hr and 108 hr after the attack as determined by ELISA. The Mn-SOD levels are also increased in the serum of patients with epithelial ovarian cancer and it is a good marker for detecting and monitoring this cancer. Mn-SOD may play an important role in the ischemic and cancer tissues.
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PMID:[Superoxide dismutases: significances in aging, diabetes, ischemia and cancer]. 223 47


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