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)

Quantitative and qualitative changes of serum proteins, apart from glycation, have not been sufficiently studied in streptozotocin-induced diabetic rats (D), the most common experimental model for diabetes. Thus, we decided to analyze the serum of diabetic rats by concanavalin A-blotting in comparison with rats with acute inflammation induced by fermented yeast (Y), in which characteristic alterations of serum proteins have been described. Two months after the streptozotocin treatment, the blood glucose levels were highly elevated (456+/-24 vs. 124+/-10 mg/dl, p<0.001, n=12), the body weight was significantly lower than normal (279+/-10 vs. 392+/-6 g, p<0.001, n=12), and serum proteins appeared to be highly glycated (p<0.001) when analyzed by the fructosamine assay, without any significant change in the total serum protein concentration. Analysis by concanavalin A-blotting, revealed a significant decrease of alpha1-inhibitor-3 (alpha1-I3, p<0.05) and an increase of the beta chain of haptoglobin (beta-Hp, p<0.05) in both D and Y rats (n=3) compared with control animals. However, acute inflammation caused a marked rise of two prominent acute phase proteins, alpha2-macroglobulin and hemopexin, which did not change appreciably in diabetic rats. Further work will be necessary to evaluate the physiopathological significance of these phenomena which could result from changes of both concentration and glycosylation of the aforementioned proteins.
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PMID:Changes of acute-phase proteins in streptozotocin-induced diabetic rats. 1107 99

Type 2 diabetes is characterized by increased acute phase serum proteins. We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years, glycosylated hemoglobin [HbA(1c)] 8.9% +/- 0.2%, body mass index [BMI] 30.9 +/- 0.8 kg/m(2), duration 5.9 +/- 1.3 years) participated in the study. They were previously treated either with diet alone or in combination with 1 oral antihyperglycemic medication. After a period of at least 4 weeks run-in on diet only, the patients were randomized to pioglitazone, glibenclamide, or placebo. Blood samples were taken before the treatments and at the end of the 6-month therapy. Basal C-reactive protein (CRP) level was related to acylation-stimulating protein (ASP) concentration (r =.55, P <.01), and many acute phase serum protein concentrations were associated with each other. The treatment reduced HbA(1c) level in the pioglitazone (from 9.1 +/- 0.3% to 8.0 +/- 0.5%, P <.05) and glibenclamide (from 8.9 % +/- 0.3% to 7.7% +/- 0.2%, P <.05) groups. Glibenclamide treatment was associated with a reduction in alpha-1-antitrypsin (P <.05), ceruloplasmin (P <.01), and complement C3 protein (C3) (P <.05). Although ASP did not change significantly in any of the treatment subgroups, in the whole patient population, the change in HbA(1c) during the treatments correlated positively with the change in ASP, (r =.43, P <.05). The changes in many acute phase serum proteins and ASP were related to each other. In conclusion, (1) inflammatory factors and complement activation are associated in patients with type 2 diabetes, and (2) changes in hyperglycemia are related to changes in the concentration of the complement activation product, ASP.
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PMID:Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes. 1123 Jul 79

Methylglyoxal (MG), an alpha-dicarbonyl compound, can be produced in vivo by several metabolic pathways and the Maillard reaction. It reacts rapidly with proteins to form advanced glycation end products or AGEs. We previously isolated and characterized a blue fluorescent product of the reaction between MG and arginine, which we named argpyrimidine. We found that argpyrimidine was stable to acid hydrolysis, which allowed us to hydrolyze tissue proteins with 6 N HCl and quantify argpyrimidine by high-performance liquid chromatography. Here we report argpyrimidine concentrations in human lens and serum proteins as determined by HPLC. We have also measured pentosidine, a fluorescent AGE derived from pentose sugars, and compared the concentrations of pentosidine and argpyrimidine. We found two- to threefold higher argpyrimidine concentrations in diabetic serum proteins than in nondiabetic controls (9.3 +/- 6.7 vs 4.4 +/- 3.4 pmol/mg). We found a significant correlation (P = 0.0001) between serum protein argpyrimidine and glycosylated hemoglobin. Argpyrimidine concentrations were approximately seven times greater in brunescent cataractous lenses than in aged noncataractous lenses. Pentosidine concentrations in serum and lens proteins were much lower than argpyrimidine concentrations; in general, argpyrimidine levels were 10--25 times higher than pentosidine. Results from our study confirm that MG-mediated arginine modifications occur in vivo and provide a method for assessing protein-arginine modification by MG in aging and diabetes.
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PMID:Chromatographic quantification of argpyrimidine, a methylglyoxal-derived product in tissue proteins: comparison with pentosidine. 1123 39

To determine if there is any difference in pancreatic function after pylorus-preserving pancreatoduodenectomy(PPPD) according to the type of pancreatoenterostomy [pancreatojejunostomy (P-J) or pancreatogastrostomy (P-G)], we evaluated the long-term functional status of 34 patients who underwent PPPD and survived for more than 1 year without clinical evidence of recurrence. Altogether 20 patients underwent P-J and 14 P-G. To compare the two groups, we analyzed the (1) general nutritional status; (2) quality of life using three scoring systems; (3) gastrointestinal symptoms; and (4) pancreatic exocrine function by the stool elastase I test and endocrine function by oral glucose tolerance test (GTT). After PPPD, body weight decreased in both groups, with no difference between the two groups. No statistical differences were found in triceps skinfold thickness or serum protein/albumin. Regarding the quality of life and postoperative gastrointestinal symptoms, there were no differences between the two groups except steatorrhea. There were 4 mild and 15 severe cases of pancreatic exocrine insufficiency among those who underwent P-J, whereas all of the patients who underwent P-G showed severe pancreatic insufficiency. On GTT, excluding preoperative diabetes patients, 43.8% (7/16) of the P-J group had abnormal results after surgery, whereas 75.0% (9/12) of the PG group had an abnormal postoperative GTT (p = 0.11). Severe exocrine and endocrine pancreatic insufficiency developed after PPPD in both the P-J and P-G groups, but there was more functional deterioration in the P-G group than in the P-J group. General nutritional status and quality of life were not affected by the pancreatoenterostomy method in either group.
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PMID:Comparison of the functional outcome after pylorus-preserving pancreatoduodenectomy: pancreatogastrostomy and pancreatojejunostomy. 1186 76

Elevated blood viscosity is a predictor of cardiovascular disease. The major determinants of blood viscosity are hematocrit and plasma viscosity. Plasma triglycerides elevate plasma viscosity; however, the contribution of plasma triglycerides to blood viscosity after adjustment for other major covariates has not been reported. This cross-sectional study of 257 adult subjects evaluated the associations between fasting plasma lipids, fibrinogen, total serum protein, hematocrit and blood viscosity. Blood viscosity was measured at 37 degrees C with a coaxial cylinder microviscometer at shear rates of 100 and 1 s(-1). Blood viscosity values are reported both as uncorrected measurements and measurements corrected to a hematocrit of 45% by a regression equation. Uncorrected blood viscosity at a shear rate of 100 s(-1) was significantly associated with triglycerides, fibrinogen, high density lipoprotein (HDL) cholesterol, total serum protein, and hematocrit using stepwise multivariate regression analysis. When corrected blood viscosity at 100 s(-1) was the dependent variable, there were statistically significant associations with triglycerides, HDL cholesterol, and total serum protein. Corrected blood viscosity at 1 s(-1) was significantly associated with triglycerides, fibrinogen, total serum protein, and an indicator variable for diabetes mellitus. This study supports an additional mechanism whereby triglycerides may contribute to cardiovascular risk.
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PMID:Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: triglycerides and blood viscosity. 1188 28

Despite improvements in dialysis therapy, the mortality rate of patients with end stage renal disease (ESRD) has remained high. A relatively high proportion of uremic patients dies within one year after the initiation of dialysis treatment. The aim of this study was to evaluate predictors for this early mortality in patients with ESRD. A total of 66 uremic patients were included in the study. Patients were divided in those who survived < 1 year (n = 17) and those who survived > or = 1 year (n = 49). We compared the prevalence of diabetes and hypertension and of vascular diseases as well as the prevalence of heart insufficiency (EF < 30%) and left ventricular hypertrophy (LVH). Additionally, we estimated the laboratory parameters serum creatinine, creatinine clearance, BUN, cholesterol, triglycerides, fibrinogen, serum protein, serum albumin and hemoglobin, and evaluated the indications for the initiation of dialysis therapy in both patient groups. The patients with survival < 1 year were significantly older (64+/-12 vs. 54+/-14 years, p<0.01) and showed a lower BMI (22+/-3 vs. 25+/-3, p<0.01) than those who survived > 1 year. The prevalence of diabetes (70% vs. 31%, p<0.05), cardiac insufficiency (70% vs. 16%, p<0.025), cardiovascular disease (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%, p<0.05) was significantly higher in the patients with early mortality. The prevalence of hypertension was similar in both groups, however, the prevalence of LVH was significantly higher in the patients who survived < 1 year (88% vs. 37%, p<0.05). Laboratory parameters were not significantly different in the two groups of patients, with the exception of serum albumin, which was significantly lower in the patients with early mortality (3.5+/-0.6 vs. 3.9+/-0.4 g/l, p<0.02). Hyperhydration was the most common indication for the start of dialysis in patients with early mortality (59% vs. 13%, p<0.025). Cardiac insufficiency was the most common cause of death in these subjects (n = 10, 59%). Six individuals (12%) died within four weeks after initiating dialysis therapy. Thus, there are several predictors for early mortality in end-stage renal disease patients, including high age, low BMI, the presence of diabetes, coronary heart disease, heart insufficiency and LVH, as well as low serum albumin levels. A relatively high percentage of patients die shortly after the start of dialysis therapy. Heart insufficiency is the most common cause of early death in these patients.
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PMID:Predialysis management and predictors for early mortality in uremic patients who die within one year after initiation of dialysis therapy. 1207 93

Although there are many investigations on protein glycation in diabetic patients, many detailed studies are needed on this subject. In this study, the correlation between red cell membrane and serum protein glycation was investigated in NIDDM. The relation of membrane glycation to intracellular Na(+) and K(+) levels was also considered. Forty patients with NIDDM and 22 healthy subjects were included in the study. The membrane proteins were isolated, and total protein (TP(m)) and fructosamine (FA(m)) levels were determined. Serum glucose, fructosamine (FA(s)) and total protein (TP(s)) levels were also measured. HbA(1C), red blood cell (RBC) and reticulocyte (RET) counts in whole blood were made in all samples. NA(+) and K(+) levels of both serum and RBC were determined. The patient group had lower levels of K(+)(RBC) (P<.001) and Na(+)(s) (P<.05) and RBC count (P<.05), and higher levels of FA(m) (P<.001), Na(+)(RBC) (P<.01), K(+)(s) (P<.01), glucose (P<.001) and HbA(1C) (P<.001) than those of controls. The ratios of FA(s)/TP(s) (P<.001) and FA(m)/TP(m) (P<.001) were higher in patients than in control. As a result, HbA(1C) levels and the ratio of FA(m)/TP(m) were high in NIDDM patients (P<.001) and these patients have slight negative correlations in FA(m)/TP(m) and FA(s)/TP(s) (P<.05). On the other hand, that there is no correlation between RBC membrane protein glycation and RBC Na(+) and K(+) levels may be caused by the fact that the membrane protein glycation is lower than that of other soluble proteins and that the membrane proteins are functional with respect to Na(+)-K(+) transport.
J Diabetes Complications
PMID:Erythrocyte membrane glycation and NA(+)-K(+) levels in NIDDM. 1220 81

This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.
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PMID:Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes. 1288 21

In 1959 and 1960, during the annual survey conducted by the Federal Northern Health Services in the area of the Northwest Passage, the diet and living conditions of some 1500 Eskimos who live in this area were studied and blood and urine samples were obtained from 40-50% of this population. Hemoglobin, blood cell morphology, serum protein-bound iodine, serum proteins, serum lipids and serum total cholesterol estimations, urinalyses, and agglutination studies for brucellosis were carried out. Hemoglobin levels were in the normal range; however, increased contact with civilization appeared to be associated with lower hemoglobin levels. Eleven per cent of the Eskimos showed eosinophilia. Serum proteins were normal. Serum lipids and serum cholesterol levels were higher in Eskimo children living in a government residential school than in a comparable group living on the Barren Lands. Serum protein-bound iodine levels were in the upper euthyroid range. Diabetes mellitus occurs among Eskimos. Sporadic cases of brucellosis also occur.
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PMID:THE ESKIMOS OF THE NORTHWEST PASSAGE: A SURVEY OF DIETARY COMPOSITION AND VARIOUS BLOOD AND METABOLIC MEASUREMENTS. 1424 93

One of the major difficulties in mining low abundance biomarkers from serum or plasma is due to the fact that a small number of proteins such as albumin, alpha2-macroglobulin, transferrin, and immunoglobulins, may represent as much as 80% of the total serum protein. The large quantity of these proteins makes it difficult to identify low abundance proteins in serum using traditional 2-dimensional electrophoresis. We recently used a combination of multidimensional liquid chromatography and gel electrophoresis coupled to matrix-assisted laser desorption/ionization-quadrupole-time of flight and Ion Trap liquid chromatography-tandem mass spectrometry to identify protein markers in sera of Alzheimer's disease (AD), insulin resistance/type-2 diabetes (IR/D2), and congestive heart failure (CHF) patients. We identified 8 proteins that exhibit higher levels in control sera and 36 proteins that exhibit higher levels in disease sera. For example, haptoglobin and hemoglobin are elevated in sera of AD, IR/D2, and CHF patients. The levels of several other proteins including fibrinogen and its fragments, alpha 2-macroglobulin, transthyretin, pro-platelet basic protein, protease inhibitors clade A and C, as well as proteins involved in the classical complement pathway such as complement C3, C4, and C1 inhibitor, were found to differ between IR/D2 and control sera. The sera levels of proteins, such as the 10 kDa subunit of vitronectin, alpha 1-acid glycoprotein, apolipoprotein B100, fragment of factor H, and histidine-rich glycoprotein were observed to be different between AD and controls. The differences observed in these biomarker candidates were confirmed by Western blot and the enzyme-linked immunosorbent assay. The biological meaning of the proteomic changes in the disease states and the potential use of these changes as diagnostic tools or for therapeutic intervention will be discussed.
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PMID:Mining biomarkers in human sera using proteomic tools. 1473 Jun 86


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