Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations in trace elements and mineral homeostasis have been documented both in insulin-dependent diabetes mellitus and non-insulin dependent diabetes mellitus. No data are available about trace elements in fibrocalculous pancreatic diabetes, a unique form of secondary diabetes mellitus. This study evaluated the plasma concentrations of copper, zinc and magnesium in this form of diabetes. Twenty-five patients (9 men and 16 women) with fibrocalculous pancreatic diabetes and 25 healthy non-diabetic subjects (16 men and 9 women) were studied. Patients with overt nephropathy were excluded. Plasma copper, zinc, and magnesium levels were analyzed using a GBC 902 double beam absorption spectrophotometer. The effect of glycemic control, microalbuminuria, sex and modality of treatment received on the plasma levels of copper, zinc and magnesium was assessed. Results of the study revealed that plasma copper, zinc, and magnesium levels were comparable between patients with fibrocalculous pancreatic diabetes and control subjects. Plasma copper levels were significantly higher in patients with controlled diabetes (16.15 +/- 0.67 micromol L(-1)) as compared to those with uncontrolled diabetes (13.75 +/- 0.61 micromol L(-1)) and healthy controls (13.91 +/- 0.55 micromol L(-1)). This merits further investigation. Microalbuminuria, modality of treatment received and sex did not influence the levels of these elements in fibrocalculous pancreatic diabetes.
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PMID:Copper, zinc and magnesium levels in fibrocalculous pancreatic diabetes. 1102 52

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94

Low density lipoprotein (LDL) oxidation is a crucial step in the atherosclerotic process. High density lipoprotein (HDL)-associated enzymes such as paraoxonase could exert a protective effect on LDL oxidation in the arterial wall, an effect which could be impaired in Type 2 diabetes mellitus (T2DM). We studied copper-induced oxidation in LDL and HDL isolated from 17 T2DM patients with fair glycaemic control and HDL-cholesterol within normal range and 17 healthy normolipidaemic control subjects. To evaluate the effect of HDL on LDL oxidation in diabetic and control subjects, we assessed copper-induced oxidation in HDL/LDL mixtures, with each lipoprotein isolated from the same subject. Relationships with HDL chemical composition, alpha-tocopherol content and serum paraoxonase activity were investigated. Oxidation was promoted by lipoprotein incubation with copper and then thiobarbituric acid reactive substances (TBARS), conjugated diene production and electrophoretic mobility in agarose gel were measured. In T2DM subjects HDL oxidation was higher than in controls. However, HDL from diabetics was as effective as control HDL to inhibit LDL oxidation. Neither HDL chemical composition nor serum paraoxonase activity showed any difference as compared to control subjects. In contrast, HDL from T2DM subjects showed a higher alpha-tocopherol content which positively correlated with HDL oxidability. Paraoxonase activity positively and strongly correlated with HDL inhibitory effect on LDL oxidation in patients and controls belonging to the heterozygous activity phenotype. Besides, LDL oxidability showed no differences between patients and controls. These results suggest that fairly-controlled T2DM patients with HDL-cholesterol levels within normal range show: 1) normal HDL ability to inhibit LDL oxidation related to normal paraoxonase activity; 2) higher HDL oxidability in spite of its high alpha-tocopherol content, which could favour tocopherol-mediated peroxidation and 3) normal LDL oxidability possibly due to the lack of significant lipoprotein structural alterations.
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PMID:HDL oxidability and its protective effect against LDL oxidation in Type 2 diabetic patients. 1134 63

The purpose of the present study was to investigate the casting accuracy and the dimensional change of experimental titanium-copper alloys (3.0 and 5.0 mass% Cu; hereafter, only "%" will be used) and to compare the findings with those of pure titanium. Castings were made using an argon-arc melting/pressure difference-casting unit. The fit of the metals cast in both full crown and MOD inlay dies was evaluated by measuring the distance between the shoulder margin and the cervical shoulder of the die. The changes in the inner diameter of castings were determined. In addition, surface roughness measurements inside the castings were carried out using a conventional profilometer, and thermal expansion measurements were made on cast cylindrical specimens using a differential dilatometer. There were no significant differences in dimensional change between pure titanium and the titanium-copper alloys. The fit of the titanium-copper alloys was inferior to pure titanium. The results of surface roughness measurements showed significance differences between the roughness of the pure titanium and titanium-copper alloys.
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PMID:Casting accuracy of experimental Ti-Cu alloys. 1144 85

The newly inbred Cohen diabetic rat is an exceptional experimental model of diet-induced type 2 diabetes mellitus that is the result of secondary inbreeding nearly 30 years after it originally had been established. Animals from the original colony were selectively inbred by stringent criteria for 10 additional generations, bringing overall inbreeding to >50 generations. The metabolic phenotypes of the resulting contrasting strains, designated as the Cohen diabetic-sensitive (CDs) and -resistant (CDr) rats, were characterized. The phenotype of the CDs strain that was fed a regular diet consisted of fasting normoglycemia, normal glucose tolerance to intraperitoneal glucose loading, normal fasting insulin levels, and a normal insulin response to glucose loading. In contrast, CDs rats that were fed a custom-prepared high-sucrose low-copper diabetogenic diet became overtly diabetic: fasting glucose levels were normal or elevated, and the blood glucose insulin response to glucose loading was markedly abnormal. CDr rats that were fed a regular or diabetogenic diet did not develop diabetes and maintained normal glucose tolerance and insulin secretion. A striking sex difference was observed in CDs rats that were fed a diabetogenic diet: males had a lower growth rate and a more severe glucose intolerance pattern than females. Gonadectomy shortly after weaning did not prevent the development of the diabetic phenotype in its early phase in either sex but markedly attenuated its expression in males at a later phase, abolishing the sex differences. Alternate-day feeding, as opposed to daily feeding, also attenuated the metabolic phenotype in males. The development of the diabetic phenotype in CDs rats that were fed a diabetogenic diet was not accompanied by obesity or hyperlipidemia. The genetic profile of the strains was established using 550 microsatellite markers evenly distributed throughout the rat genome. The rate of homozygosity within strain was > or = 96%. The rate of polymorphism between the contrasting strains was 43%. We conclude that the metabolic phenotypes of the rebred colony of CDs and CDr rats and their genetic makeup render the Cohen diabetic rat a useful experimental model that is highly suitable for studying the interaction between nutritional-metabolic environmental factors and genetic susceptibility (sensitivity and resistance) for the development of type 2 diabetes. The model is also distinctively useful for investigating the effect of sex on the expression of the diabetic phenotype.
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PMID:The newly inbred cohen diabetic rat: a nonobese normolipidemic genetic model of diet-induced type 2 diabetes expressing sex differences. 1167 30

A review of the meeting Protein Phosphatases, FASEB Summer Research Conference, Copper Mountain, CO, 23 to 28 July 2000. Shenolikar and Brautigan summarize the key issues discussed at the conference on protein phosphatases of the Federation of American Societies for Experimental Biology (FASEB). A theme of the meeting was how basic research in the field of protein phosphatases has led to better understanding and treatments for human disease, including type 2 diabetes and obesity. A second important issue presented related to identification and characterization of various phosphatase-binding proteins that regulate phosphatase action.
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PMID:Meeting report: targeting protein phosphatases-medicines for the new millenium. 1175 18

This study evaluated the influence of the pulp protection technique on clinical performance of amalgam restorations after three years, with particular reference to post-operative sensitivity and secondary caries. One hundred and twenty (120) Class II amalgam restorations (68 premolars, 52 molars; 78 MOD, 42 OD/MO) were placed in 30 participants (four restorations per participant). The restorations were divided into four groups according to the pulp protection technique used: copal varnish; 2% neutral sodium fluoride; adhesive resin and no pulp protection. The parameters evaluated were post-operative sensitivity, staining of the dental structure, tooth vitality, partial or total loss of the restoration and secondary caries. One hundred and eight (108) restorations were available for evaluation after three years. No partial or total loss of restorations had occurred; all teeth were vital, no tooth structure staining or secondary caries was detected in any of the restored teeth. Post-operative sensitivity was observed only in two restorations at baseline and at seven-days. The three-year clinical performance of teeth restored with a high copper dispersed phase amalgam was not affected by the choice of pulp protection technique.
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PMID:Effect of pulp protection technique on the clinical performance of amalgam restorations: three-year results. 1212 Jul 67

This study describes the occurrence of 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one (HMDP) in plasma obtained from normal subjects and patients with type 2 diabetes. We have shown previously that HMDP is a novel hydrophilic hydroperoxide formed in the in vitro Maillard reaction that could be analyzed using ultrasensitive chemiluminescence detection-high-performance liquid chromatography (CL-HPLC). The HMDP concentration was 273+/-227 nmol/l in normal subjects and 656+/-535 nmol/l in patients with diabetes. The HMDP concentration was proportional to the plasma glucose concentration level (r=0.640; P<0.01) but not with the glycated hemoglobin level. To investigate the in vivo effects of HMDP, a range of concentrations of the compound was incubated for different time periods with human serum albumin and lipoproteins. HMDP was found to induce denaturation of these macromolecules by modifying lysine residues and causing cross-linking and polymerization of proteins. In the presence of metal ions such as iron and copper, HMDP induced peroxidative degradation of lipoprotein lipids as measured by an elevation in thiobarbituric acid reactive substances (TBARS) concentration. These results suggested that HMDP is produced as a consequence of both hyperglycemia and increased oxidative stress, and may have the potential to contribute to the pathogenesis of arterial complications in diabetes mellitus.
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PMID:The occurrence of a novel hydrophilic hydroperoxide, 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one, as a reactive glycation product in human plasma. 1238 41

The aim of the present study was to investigate whether altered serum total sialic acid (TSA), lipid-associated sialic acid (LSA), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), iron (Fe), and magnesium (Mg) levels had an interactive connection with diabetes and also whether they were correlated with each other in diabetic patients. Two study groups (control and type 2 diabetic subjects) were included. Two hundred patients (108 female and 92 male), diagnosed and treated for type 2 diabetes in the Yuzuncu Yil University Hospital (Van, Turkey), were selected consecutively to represent type 2 diabetic patients. Fifty healthy individuals (29 female and 21 male) served as the control group matched for age, sex, body mass index, and smoking status were selected from hospital staff and other outpatient clinics. All participants had not taken vitamin or mineral supplements for at least 2 wk before sampling. Blood samples were drawn after an overnight fasting in both groups for the determination of serum glucose, TSA, LSA, Cu, Zn, Mn, Cr, Fe, and Mg. It was found that diabetics had higher TSA, LSA, Fe, Mn, Fe/Zn, and Cu/Zn levels, and lower Zn and Mg levels than those of controls. Although, Cu levels were higher, and Cr levels were lower in total and male diabetic patients, they were not different in female diabetic patients than in controls. The Cu/Fe ratio was lower in total and female diabetic patients, but not different in male diabetic patients than controls. The Zn/Cr ratio, on the other hand, was not different in diabetics than in controls. There was only a positive correlation between Fe-Mn levels in male diabetic patients. There was a negative correlation in LSA-Mn, Fe-Cu, Cu-Fe/Zn, and Mn-Cu/Zn levels in total diabetic patients. There was a positive correlation in TSA-Cr, TSA-Mg, LSA-Cu/Fe, LSA-Zn/Cr levels, and a negative correlation in TSA-Cu/Zn, LSA-Mn, Fe-Cu, Mn-Cu, Cu-Fe/Zn, Fe-cholesterol, and Cr-cholesterol in female diabetic patients. Our results showed that TSA, LSA, and selected minerals have interactive connections with diabetes mellitus (DM). There are also many sex-related positive or negative correlations between the altered parameters in diabetic patients. These parameters might be used as diagnostic index in patients with DM.
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PMID:Serum sialic acid levels and selected mineral status in patients with type 2 diabetes mellitus. 1297 87

Obesity is accompanied by a high incidence of atherosclerosis, arterial hypertension and non-insulin dependent diabetes mellitus in the pathogenesis of which is associated with oxygen-derived free radicals. The aim of the study was to compare blood oxidation status in obese women without coexisting diseases and in healthy women with normal body mass index (BMI). Studies were performed in 29 premenopausal obese (BMI 35.79 +/- 4.62 kg/m2) and 31 lean (BMI 22.29 +/- 1.05 kg/m2) women. Plasma lipid profile, activities of antioxidant enzymes: copper/zinc (Cu/ZnSOD) and manganese-containing superoxide dismutase (MnSOD) and glutathione peroxidase (GSH-Px), as well as concentrations of malondialdehyde (MDA)--a product of lipid peroxidation, were examined. In obese women there were significantly higher concentrations of total cholesterol (5.02 +/- 0.83 vs. 4.15 +/- 0.43 mmol/l; p < 0.05), LDL-cholesterol (3.12 +/- 0.90 vs. 2.35 +/- 0.42 mmol/l; p < 0.05) and triglycerides (1.72 +/- 0.85 vs. 1.02 +/- 0.18 mmol/l; p < 0.01), while HDL-cholesterol level was lower (1.01 +/- 0.16 vs. 1.25 +/- 0.2 mmol/l; p < 0.05). Moreover, in comparison to the control group, obese women showed increased activities of plasma MnSOD (6.72 +/- 1.43 vs. 4.99 +/- 0.58 NU/ml; p < 0.05) and erythrocyte GSH-Px (35.38 +/- 10.31 vs. 19.15 +/- 7.12 mumol NADPH2/g Hb/min; p < 0.001), and concentrations of plasma MDA (2.93 +/- 0.53 vs. 2.16 +/- 0.31 mumol/l; p < 0.05) and erythrocyte MDA (2.24 +/- 0.30 vs. 1.59 +/- 0.36 mumol/g Hb; p < < 0.001). There were no differences between the two groups in activities of plasma and erythrocyte Cu/ZnSOD. In conclusion, the results demonstrate disturbances in oxidation status in premenopausal obese women with abnormal lipid profile, which may indicate the association between oxygen-derived free radicals and the increase in the incidence of obesity-related diseases.
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PMID:[Assessment of blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde concentration as oxidation status parameters in obese women]. 1468 7


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