Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.
 ...
PMID:Vascular filtration function in galactose-fed versus diabetic rats: the role of polyol pathway activity. 211 13

Macrophages internalize and degrade proteins modified by advanced glycosylation end products (AGEs) via a specific receptor (AGE-R). Chemical cross-linking studies with AGE-bovine serum albumin have demonstrated that the molecular weight of this receptor is approximately 90,000. We previously established that the binding constant (Ka) of this receptor site for the chemically synthesized model AGE, 2-(2-furoyl)-4(5)-(2-furanyl)-1H- imidazole-butyric acid (FFI-BA), on cells of the mouse macrophagelike cell line RAW 264.7 is identical to that for AGE proteins. Therefore, FFI was used as an affinity matrix in the first purification step of the AGE-R. The membranes of RAW 264.7 cells were solubilized in octyl-beta-glucoside and subjected to affinity chromatography on FFI-sepharose and gel permeation on Superose 6 fast protein liquid chromatography. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis analysis of this material revealed a high enrichment of a 90,000-Mr protein that had AGE binding activity. Approximately 25% of the protein at this step was the 90,000-Mr protein. The 90,000-Mr membrane protein was purified to homogeneity by rechromatographing the material on Superose 12 in the presence of SDS before and after reduction with 2-mercaptoethanol. After these harsh conditions, the 90,000-Mr protein lost AGE binding activity. Additional cross-linking studies on human peripheral monocytes revealed an AGE-R protein of identical size to that on RAW 264.7 cells, suggesting the relatively highly conserved nature of this molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Dec
PMID:Isolation of surface binding protein specific for advanced glycosylation end products from mouse macrophage-derived cell line RAW 264.7. 217 9

The present study was undertaken to compare the changes in islet cell antibodies (ICA), islet cell surface antibodies using rat insulinoma cells (RINr-ICSA), and anti-bovine serum albumin antibodies (BSA-Ab) in the clinical course of type 1 (insulin-dependent) diabetes. Sera were obtained from 57 patients with type 1 diabetes and 47 normal controls. ICA, RINr-ICSA and BSA-Ab were detected by an enzymatic immunohistochemical method, an indirect immunofluorescence method and an enzyme-linked immunosorbent assay, respectively. The incidence of ICA significantly decreased with the duration of diabetes: less than 1 year: 5/6 (83%); 1-2 years: 3/6 (50%); 2-3 years; 2/6 (33%); greater than 3 years 6/39 (15%). There was a significant positive correlation between RINr-ICSA and BSA-Ab (P less than 0.05). These findings suggest that RINr-ICSA or BSA-Ab may be produced by some similar immune mechanism which is, however, different from ICA, and that they have no direct relation to the clinical course of diabetes.
Diabetes Res Clin Pract 1990 Jul
PMID:Comparison of islet cell antibodies, islet cell surface antibodies and anti-bovine serum albumin antibodies in type 1 diabetes. 222 20

Serum total calcium concentrations (CaT) were increased, ionized calcium concentrations (CaI) normal, and the CaI/CaT ratios decreased in 125 geriatric diabetics as compared with 379 non-diabetic controls. In the whole population of 558 consecutive geriatric inpatients, the CaI/CaT ratios were inversely correlated with body weight, diastolic blood pressure and plasma glucose. The findings and calculations help to explain some inconsistencies and discrepancies in previous studies concerning calcaemia in diabetes, hypertension and the 'metabolic syndrome' of clustered risk factors for cardiovascular diseases. They also demonstrate that CaT and the 'correction' of CaT for serum albumin concentration can be biased in diabetes and other conditions closely associated with cardiovascular risks. Increased serum free fatty acids could at least in part explain low ratios.
 ...
PMID:Low serum ionized to total calcium ratio: association with geriatric diabetes mellitus and with other cardiovascular risk factors? 227 24

To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, 1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, 2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, 3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and 4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats. These observations indicate that diabetes-induced increases in regional blood flow, 131I-BSA permeation, GFR, and urinary protein excretion can be markedly reduced or normalized by consumption of myo-inositol-supplemented diets that raise plasma myo-inositol levels approximately fivefold. The failure of the 2% myo-inositol diet to normalize GFR and blood flow and albumin permeation in several tissues despite markedly elevated plasma myo-inositol levels and normal or elevated tissue myo-inositol levels indicates that if vascular functional changes in these tissues are linked to altered myo-inositol levels, they are resistant to normalization by elevation of plasma myo-inositol levels. These results suggest that other factors independent of changes in relative or absolute tissue myo-inositol levels may play an important role in the pathogenesis of diabetes-induced vascular functional changes in these tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1990 Mar
PMID:Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol. 230 93

Logistic regression analysis was applied to a sample of more than 12,000 hemodialysis patients to evaluate the association of various patient descriptors, treatment time (hours/treatment), and various laboratory tests with the probability of death. Advancing age, white race, and diabetes were all associated with a significantly increased risk of death. Short dialysis times were also associated with high death risk before adjustment for the value of laboratory tests. Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. About two thirds of patients had low albumin. These findings suggest that inadequate nutrition may be an important contributing factor to the mortality suffered by hemodialysis patients. The relative risk profiles for other laboratory tests are presented. Among these, low serum creatinine, not high, was associated with high death risk. Both serum albumin concentration and creatinine were directly correlated with treatment time so that high values for both substances were associated with long treatment times. The data suggest that physicians may select patients with high creatinine for more intense dialysis exposure and patients with low creatinine for less intense treatment. In a separate analysis, observed death rates were compared with rates expected on the basis of case mix for these 237 facilities. The data suggest substantial volatility of observed/expected ratios when facility size is small. Nonetheless, a minority of facilities (less than or equal to 2%) may have higher rates than expected when compared with the pool of all patients in this sample. The effect of various laboratory variables on mortality is substantial, while relatively few facilities have observed death rates that exceed their expected values. Therefore, we suggest that strategies designed to improve the overall mortality statistic for dialysis patients in the United States would be better directed toward improving the quality of care for all patients, particularly high-risk patients, within their usual treatment settings rather than trying to identify facilities with high death rate for possible regulatory intervention.
 ...
PMID:Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. 233 68

Lymphocytic choriomeningitis virus (LCMV) infection prevents the usual insulin-dependent diabetes mellitus of aged BB rats (Dyrberg, Schwimmbeck & Oldstone, 1988; Schwimmbeck, Dyrberg & Oldstone, 1988). In this study earlier observations are extended by noting that LCMV infection substantially alters the immune responsesof BB diabetic-prone (dp) rats. The control, uninfected rats make vigorous primary and secondary antibody responses when challenged with keyhole limpet haemocyanin (KLH), human immunoglobulin (HuIg) or sheep red blood cells (SRBC). Such rats fail to mount a primary response to bovine serum albumin (BSA) but do produce a moderate secondary response. They mount good antibody responses to LCMV but fail to generate either primary or secondary LCMV-specific cytotoxic T-lymphocyte (CTL) responses or CTL responses to Pichinde virus. In contrast, BB dp rats acutely infected with LCMV generate no primary immune responses to SRBC, KLH or BSA and only meager responses when challenged with HuIg. They mount secondary responses to KLH, HuIg and BSA that approximate those of their uninfected litter mates, but have a comparatively lower response to SRBC. LCMV binds to and infects lymphocytes of the BB dp rat. Binding is enhanced over that observed with lymphocytes from BB diabetic-resistant (dr) rats, which are able to generate CTL immune responses to LCMV and Pichinde viruses. Hence, lymphocytes from BB dp rats are uniquely susceptible to binding and replication of LCMV. During the acute stage of LCMV infection, a general primary T-cell immunosuppression occurs with respect to a variety of viral and non-viral antigens. Over time, responsiveness to T-cell dependent antigens returns except for the ability to generate CTL responses to LCMV or the autoimmune response(s) required to cause insulin-dependent diabetes mellitus.
 ...
PMID:Inhibition of diabetes in BB rats by virus infection. II. Effect of virus infection on the immune response to non-viral and viral antigens. 233 72

Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.
 ...
PMID:Multiple fatty acid binding to albumin in human blood plasma. 233 79

This study has examined glycation of serum albumin and its role in evolving diabetic proteinuria. Renal clearances of endogenous glycated and nonglycated albumin were studied in groups of normal and streptozotocin-induced diabetic Wistar-Kyoto rats over a 32 week period. Concentrations of glycated and nonglycated albumin in serum and urine were measured by rat albumin radioimmunoassay following separation on m-aminophenylboronate affinity columns. Levels of glycated serum albumin in diabetic rats were significantly higher than in normal rats (5.9 +/- 0.7% vs 4.4 +/- 0.3%, P less than 0.05). Median total urinary albumin excretion increased from 120 micrograms/24 h at baseline to 879 micrograms/24 h (P less than 0.05) 28-32 weeks after induction of diabetes. The renal clearance of glycated albumin was approximately twice as great as that of nonglycated albumin in both normal (P less than 0.01) and diabetic (P less than 0.01) rats. However, the glycated albumin/nonglycated albumin clearance ratio in diabetic rats did not correlate with duration of diabetes or with the level of albuminuria. These results indicate that glycation of albumin does not contribute disproportionately to the development of proteinuria in the diabetic rat, during which median renal albumin clearance increased 7-fold. Other factors, such as glycation of the glomerular filtration surface, may have a more important role in the pathogenesis of proteinuria in experimental diabetes.
Diabetes Res Clin Pract 1990 Mar
PMID:Longitudinal evaluation of the renal clearance of glycated albumin in the diabetic rat. 234 Jul 93

To evaluate the incidence, risk factors, and clinical course of radiocontrast nephrotoxic effects in the elderly, 183 patients aged 70 years or more undergoing 199 cardiac catheterizations were studied prospectively. Contrast nephropathy (a rise in creatinine level of greater than or equal to 44 mumol/L above baseline) occurred in 21 cases (11%). In 16 (76%) of these 21 cases, renal function returned toward baseline within several days. One patient developed transient oliguria, but no deaths were attributable to renal failure. Independent risk factors for renal dysfunction included contrast volume greater than 200 mL, serum albumin level less than 35 g/L, diabetes mellitus, serum sodium level less than 135 mmol/L, and baseline creatinine level greater than 133 mumol/L. Renal insufficiency occurred in 1.2% of patients with no risk factors, 11.2% of those with one risk factor, and more than 20% of those with two or more risk factors. Thus, the incidence and clinical course of radiocontrast nephropathy in the elderly are similar to those in younger patients. High-risk elderly patients who may benefit from more aggressive prophylaxis can be prospectively identified, but the threat of contrast nephrotoxic effects should not be considered a major contraindication to angiography in appropriately selected patients.
 ...
PMID:Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. 235 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>