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)

Amino metabolites with potential prooxidant properties, particularly alpha-aminocarbonyls, are the focus of this review. Among them we emphasize 5-aminolevulinic acid (a heme precursor formed from succinyl-CoA and glycine), aminoacetone (a threonine and glycine metabolite), and hexosamines and hexosimines, formed by Schiff condensation of hexoses with basic amino acid residues of proteins. All these metabolites were shown, in vitro, to undergo enolization and subsequent aerobic oxidation, yielding oxyradicals and highly cyto- and genotoxic alpha-oxoaldehydes. Their metabolic roles in health and disease are examined here and compared in humans and experimental animals, including rats, quail, and octopus. In the past two decades, we have concentrated on two endogenous alpha-aminoketones: (i) 5-aminolevulinic acid (ALA), accumulated in acquired (e.g., lead poisoning) and inborn (e.g., intermittent acute porphyria) porphyric disorders, and (ii) aminoacetone (AA), putatively overproduced in diabetes mellitus and cri-du-chat syndrome. ALA and AA have been implicated as contributing sources of oxyradicals and oxidative stress in these diseases. The end product of ALA oxidation, 4,5-dioxovaleric acid (DOVA), is able to alkylate DNA guanine moieties, promote protein cross-linking, and damage GABAergic receptors of rat brain synaptosome preparations. In turn, methylglyoxal (MG), the end product of AA oxidation, is also highly cytotoxic and able to release iron from ferritin and copper from ceruloplasmin, and to aggregate proteins. This review covers chemical and biochemical aspects of these alpha-aminoketones and their putative roles in the oxidative stress associated with porphyrias, tyrosinosis, diabetes, and cri-du-chat. In addition, we comment briefly on a side prooxidant behaviour of hexosamines, that are known to constitute building blocks of several glycoproteins and to be involved in Schiff base-mediated enzymatic reactions.
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PMID:The dual face of endogenous alpha-aminoketones: pro-oxidizing metabolic weapons. 1692 Apr 3

The aim of this study was to compare the nutritional status of zinc and copper in patients with and without diabetes submitted to chronic hemodialysis. Thirty-three patients with type 2 diabetes (DM group), 30 nondiabetic patients (NDM group), and 20 healthy individuals (control group) were studied. Plasma, erythrocyte, and urinary zinc and plasma copper were obtained from atomic absorption spectrophotometry and ceruloplasmin by immunonephelometry. The anthropometric parameters were similar among the groups. Plasma zinc was lower and erythrocyte zinc was higher in the DM and NDM groups in relation to the control group. No difference in urinary zinc was observed comparing the groups. Plasma copper was higher in the DM group when compared to the NDM and control groups. Ceruloplasmin was similar in the three groups. Serum urea was a positive independent determinant of plasma zinc concentrations. The determinants of erythrocyte zinc were MAMC midarm muscle circumference and Kt/V dialysis adequacy. The determinants of plasma copper concentration were serum creatinine and serum glucose. The results of this study demonstrate an alteration in the distribution of zinc in patients with chronic kidney disease (CKD) independently of the presence of DM. Also, the status of copper seems not to be influenced by CKD, but only by the metabolic derangements associated with diabetes.
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PMID:Effect of end-stage renal disease and diabetes on zinc and copper status. 1694 12

To search out novel biomarkers for monitoring diabetes prognosis, we examined the effect of hypoglycemic fungal exopolysaccharides (EPS) on the differential levels of plasma proteins in streptozotocin-induced diabetic rats. The orally administrated EPS exhibited an excellent hypoglycemic effect, lowering the average plasma glucose level, and increasing insulin secretion in diabetic rats. The 2-DE analysis of rat plasma demonstrated that about 500 visualized spots were differentially regulated, of which 20 spots were identified as principal diabetes-associated proteins. The distinct effect of diabetes induction on the pattern of rat plasma proteins includes the down-regulation of albumin, apolipoprotein E (Apo E), alpha1-inhibitor-3, fetuin beta, Gc-globulin, hemopexin, vitronectin, and transthyretin (TTR) monomer, and the up-regulation of Apo A-I, Apo A-IV, ceruloplasmin, alpha1-antitrypsin, serine protease inhibitor III, and transferrin. Those protein levels were interestingly restored to those of healthy rats by EPS treatment, although the order of magnitude of the changes differed widely. Two proteins of interest showed distinct differential expression with opposite trends: TTR tetramer was significantly down-regulated and immunoglobulin (Ig) kappa light chain was significantly up-regulated upon diabetes induction, both of which were also normalized to those of healthy groups after EPS treatment.
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PMID:Effect of fungal polysaccharides on the modulation of plasma proteins in streptozotocin-induced diabetic rats. 1694 19

In a Chinese woman who had diabetes mellitus, undetectable ceruloplasmin, hand tremor, neck dystonia, and cognitive disturbances, genetic analyses revealed a novel homozygous mutation (848G > C or W283S) in exon 5 in the ceruloplasmin gene. Another member with a milder phenotype was also affected by this mutation. The healthy sister was heterozygous at the same position. Aceruloplasminemia has not yet been reported in China. This case suggests that increased awareness should be paid to this disorder in the presence of the typical symptoms.
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PMID:Novel mutation in the ceruloplasmin gene causing a cognitive and movement disorder with diabetes mellitus. 1701 8

Previous studies about protein modulation with chemically induced models of diabetes in animals have yielded conflicting results, in that many investigators have reported different regulation patterns for the same proteins. Therefore, it is reasonable to determine biomarkers for prognosis and diagnosis of diabetes with time profiling for the candidate proteins. In this regard, we examined the influence of hypoglycemic fungal polysaccharides (EPS) on the time-dependent plasma protein alterations in streptozotocin-induced diabetic rats. The 2-DE analysis of rat plasma demonstrated that about 50 proteins from about 900 visualized spots were found to be differentially regulated, of which 20 spots were identified as principal diabetes-associated proteins. The results of time profiling revealed that most of the identified proteins showed significant alterations in a time-dependent manner during 14 days, with notable trends. Nine out of the twenty proteins displayed very similar time profiles between normal healthy and EPS-treated diabetic rats. Interestingly, the altered profiles of several proteins by diabetes induction almost returned to control levels after EPS treatments. In particular, we found a clear distinction in differential expression of oxidative stress proteins (ceruloplasmin and transferrin) and lipid metabolism related proteins (Apo A-I, Apo A-IV, and Apo E) in the STZ-induced diabetic rats. The data presented here have identified and characterized the time-dependent changes in plasma proteins associated with EPS treatment in STZ-induced diabetic rats, thereby leading to the discovery of early-response and late-response biomarkers in diabetic and EPS-treated states.
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PMID:Time-dependent plasma protein changes in streptozotocin-induced diabetic rats before and after fungal polysaccharide treatments. 1708 Oct 48

Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.
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PMID:Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic beta-cells in experimental diabetes in rats. 1718 70

Clinical research has confirmed the efficacy of several photo-chemicals in modulating oxidative stress associated with diabetes mellitus. Here we investigate the effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on antioxidant status in streptozotocin-nicotinamide-induced diabetes in rats. A single dose of streptozotocin (65 mg kg(-1) bwt) resulted in decreased insulin, hyperglycemia, increased lipid peroxidation (thiobarbituric reactive substances, lipid hydroperoxides), and decreased antioxidant levels (vitamin C, vitamin E, reduced glutathione and ceruloplasmin). The oral administration of THC (80 mg kg(-1) bwt) for 45 days to diabetic rats significantly increased plasma insulin and plasma antioxidants and significantly decreased lipid peroxidation. The positive effects of THC were better that those achieved with curcumin. The results of the study indicate that in addition to its antidiabetic effect in type 2 diabetic rats, THC has an antioxidant effect.
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PMID:Effect of tetrahydrocurcumin on plasma antioxidants in streptozotocin-nicotinamide experimental diabetes. 1733 79

The effects of oral zinc supplementation on lipid peroxidation and the antioxidant defense system of alloxan (80-90 mg/kg)-induced diabetic rabbits were examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately 2.5 kg, were allocated randomly and equally as control, diabetic, and zinc-supplemented diabetic groups. After diabetes was induced, zinc-supplemented diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO(4)) in their drinking tap water for 3 months. The feed and water consumption was higher in diabetic groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic rabbits compared to control. The blood glucose levels were higher in diabetic groups than controls. The elevated plasma malondialdehyde (MDA) levels were determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin levels in the diabetic group were decreased by the effect of diabetes but there was no difference between zinc-supplemented diabetic and control rabbits. Serum zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu) levels in sera were not different among the groups. As a result, it was concluded that daily zinc supplementation could reduce the harmful effects of oxidative stress in diabetics.
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PMID:Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits. 1744 94

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (beta-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.
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PMID:Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. 1792 55

Hereditary aceruloplasminemia (HA) is a rare inherited disease characterized by anemia, iron overload, diabetes, and neurodegeneration. HA is caused by the homozygous mutation of the ceruloplasmin (CP) gene. We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). An early diagnosis of iron overload was made in the female sibling who was subsequently treated with deferoxamine. At the age of 54, her neurologic symptoms were limited to mild akinetic signs and a history of seizures; moreover, her fasting blood glucose level never exceeded 120 mg/dL. The male sibling, who had not received any specific treatment for HA, developed severe diabetes at the age of 32 and at 48 manifested a progressively disabling neurologic disease. Possible physiopathological bases of these intrafamilial phenotypic variations are discussed.
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PMID:Aceruloplasminemia: a novel mutation in a family with marked phenotypic variability. 1820 Jun 28


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