Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of measurement of serum and urinary type IV collagen (IV-C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV-C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated.
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PMID:Serum and urinary type IV collagen concentrations in the assessment of diabetic microangiopathy. 788 78

Huge strides have been made in the molecular genetics and clinical investigation of several inherited renal diseases. In autosomal dominant polycystic kidney disease 1) the genetic localization of the defective gene that causes type 1 disease has been narrowed to 500 to 750 kb on chromosome 16; 2) cystogenesis has been associated with increased cell proliferation, continuing cyst secretion, and a defect in cell polarity; however, the mechanisms by which the genetic defects in autosomal dominant polycystic kidney disease translate into cyst formation are unknown; 3) activation of the renin system has been reported as an important potential cause of hypertension; and 4) factors that influence the progression to renal failure have been identified. In Alport's syndrome, mutations in the alpha 5 (IV) collagen gene on the X chromosome have been demonstrated that may induce defective assembly of alpha 3 (IV) chains by an unknown mechanism, which leads to the disruption of the glomerular basement membrane. In diabetic nephropathy, it has been suggested that familial factors, perhaps genetic in origin, may play an important role in its development.
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PMID:Hereditary renal diseases. 792 77

Detection of glycosylated protein in renal tissues was determined in streptozotocin (STZ)-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction. The glycosylation of extra-cellular matrix (ECM) components such as laminin and fibronectin was examined in vitro using the same method. Immunofluorescence staining of laminin or type IV collagen was also performed in renal tissues of STZ-induced diabetic rats. There was no significant difference in the intensity of NBT in renal tissues between 4 week STZ-induced diabetic rats and control rats of the same age. The intensity of NBT staining in the glomerular mesangial areas and capillary walls was marked in 12 week diabetic rats. The mean values of fructosamine measured by the NBT reaction in the glycosylated-laminin and fibronectin were increased dose dependently. In immunofluorescence, laminin and type IV collagen were observed significantly in the glomerular mesangial areas and capillary walls of 12 week diabetic rats. However, there was no significant change in renal histopathology in 4 and 12 weeks diabetic rats. It appears that the non-enzymatic glycosylation and expression of ECM components in glomeruli increased in the early stage of diabetic nephropathy prior to the appearance of marked histologic alterations. In conclusion, non-enzymatic glycosylation of glomerular structural components may play an important role in the initiation of the early stage of renal injuries in diabetes.
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PMID:Detection of glycosylated protein in glomeruli of STZ-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction. 793 13

Late stage diabetic nephropathy is histologically characterized by either diffuse or nodular expansion of the glomerular matrix. This is presumed to represent the morphological correlate for the functional impairment of the kidney. The exact matrix composition of the nodular glomerulosclerosis lesion of end-stage diabetic nephropathy is not known. Biochemical studies have provided evidence that the microfibrillar collagen type VI is increased in diabetic nephropathy. Consequently, this immunohistochemical study was designed to evaluate the extent and exact morphologic location of increased collagen VI deposition at various stages of diabetic glomerulosclerosis (GS). An irregular, sometimes spot-like staining of collagen VI was observed in diffuse GS in the mesangial portion. The uninterrupted staining which was evident along the glomerular basement membrane in normal glomeruli was discontinuous in diffusely sclerotic glomeruli. In nodular GS, the markedly increased deposition of collagen VI appeared to be evenly distributed throughout the entire nodular lesion. At the same time, mesangial staining for collagen IV was reduced in nodular GS, suggesting that in the expanded mesangial matrix collagen IV is progressively substituted by collagen VI during the transition from diffuse to nodular GS. The colocalization of PAS staining with collagen VI deposition in nodular GS suggests that the typical Kimmelstiel-Wilson lesions at least in part consist of collagen VI. Biochemical analysis confirmed the increased collagen VI deposition in glomeruli extracted from diabetic patients with nodular GS. Application of two antisera, recognizing primarily the alpha 1(VI)- and alpha 2(VI)-chains and the N-terminal part of alpha 3(VI)-chain, respectively, revealed no difference in staining pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical localization of collagen VI in diabetic glomeruli. 793 12

The pathogenesis of diabetic nephropathy is incompletely understood, but increased nonenzymatic glycation of proteins is considered an important contributory factor. Glycated albumin, which is increased in diabetic sera and is preferentially transported into the renal glomerulus, induces an increase in Type IV collagen production and a decrease in proliferative capacity by mesangial cells in culture. These effects resemble the abnormalities that characterize the glomerular mesangium in diabetes and are prevented by monoclonal antibodies that specifically react with Amadori adducts in glycated albumin. To explore the possibility that the in vitro effects of glycated albumin on mesangial cell biology pertain to the in vivo situation, we examined the effect of treatment with the A717 monoclonal antibodies on glomerular functional and structural changes in a rodent model of genetic diabetes, the db/db mouse. Weekly parenteral antibody administration reduced the elevated albumin excretion and attenuated the mesangial expansion that were observed in the untreated db/db mice that served as controls. Monoclonal antibody treatment also was shown to lower plasma concentrations of glycated albumin in diabetic mice. Thus, reducing glycated albumin concentrations and/or blocking its biologically active epitopes has a salutary influence on the pathogenesis of diabetic nephropathy. The findings indicate that glycated albumin participates in the development of the glomerular lesion in the db/db mouse, and suggest a new approach to the therapy of this complication of diabetes.
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PMID:Amelioration of diabetic nephropathy by treatment with monoclonal antibodies against glycated albumin. 793 15

Nodular intercapillary glomerulosclerosis is the most typical lesion of diabetic nephropathy (DN) and is characterized by increased extracellular matrix (ECM) and amorphous masses of mesangial matrix. The local exaggeration of these deposits results in the formation of the typical diabetic nodule. To clarify the composition of the ECM of sclerotic lesions in DN, we investigated the distribution of type III and type IV collagens and their mRNAs by immunohistochemistry and in situ hybridization, respectively. In normal renal tissues, there was no intraglomerular immunostaining for type III collagen, while strongly positive staining was found in the extraglomerular interstitium. Positive immunostaining for type IV collagen was also present in the mesangium, glomerular basement membrane (GBM), Bowman's capsule, and the vascular pole of the normal glomerulus. In DN, the nodular lesions were negative for type III collagen and strongly positive for type IV collagen. On the other hand, in the late stage of global sclerosis, both type III and type IV collagens were diffusely present in the sclerotic matrix. To determine the origins of these type III and type IV collagens in the sclerotic matrix, in situ hybridization was performed, utilizing thymine-thymine (T-T) dimerized synthetic oligonucleotides complementary to either pro alpha 1(III) chain or pro alpha 1(IV) chain mRNAs as probes. The signals were detected by enzyme immunohistochemistry using an anti-T-T antibody. Intraglomerular cells (glomerular epithelial and mesangial cells) containing type III collagen mRNA were found in DN with sclerotic lesions, but not in normal glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ localization of type III and type IV collagen-expressing cells in human diabetic nephropathy. 796 8

The development of alpha-amylase and brush-border alpha-glucosidase inhibitors is reviewed. The mode of action as well as pharmacological and pharmacodynamic properties of selected inhibitors with special regard to the most thoroughly investigated alpha-glucosidase inhibitor acarbose are discussed. Inhibition of intestinal alpha-glucosidases delays the digestion of starch and sucrose, flattens the postprandial blood glucose excursions, and thus mimics the effects of dieting on hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. Therefore, the mechanism of alpha-glucosidase inhibition represents the pharmacological optimization of the dietary principle of delayed carbohydrate absorption. In pre-clinical studies using diabetic animals the oral administration of acarbose improved the metabolic state and reduced the blood glucose area under the curve. As a consequence, the process of non-enzymatic glycation of proteins was retarded as indicated by reduced glycated haemoglobin, glomerular basement membranes or advanced glycation end-products (AGEs) in collagen. These improved biochemical parameters correlated with beneficial effects against the development of diabetic nephropathy and neuropathy. Thus, the treatment of diabetic animals with acarbose does not only improve the metabolic state but has also the potential to delay, or possibly prevent, the development of diabetic complications.
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PMID:Pharmacology of alpha-glucosidase inhibition. 800 24

Molecular organization of extracellular matrix (ECM) in the kidney may change as impairment of renal function progresses. The present immunohistochemical study of the kidney was designed to compare localization of type I, III, IV, V, and VI collagens between "Group A" (13 patients on maintenance hemodialysis due to diabetic nephropathy) and "Group B" (13 patients with diabetic nephropathy and massive proteinuria whose serum creatinine levels were 1.3 +/- 0.5 mg/dl, mean +/- SD). Nodular scleroses that were commonly observed both in Group A (87.8 +/- 10.1%) and B (80.5 +/- 17.0%) were stained in a very similar way with antibodies against collagen types IV, V, and VI. On the contrary, thickened Bowman's capsules that were observed exclusively in Group A (80.7 +/- 10.4% in Group A versus 5.7 +/- 6.2% in Group B) were stained intensely with antibodies against collagen types I and III. Normal and expanded peritubular interstitium from every group was stained with all of the above antibodies in an identical manner. Taken together, these results indicated a close relationship between severe impairment of residual renal function and a high incidence of thickened Bowman's capsule rich in type I and III collagens.
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PMID:Phenotypic expressions of type I, III, IV, V, and VI collagens in patients with diabetic nephropathy: immunohistochemical comparison between HD and non-HD patients. 802 9

High glucose directly promotes lipid peroxidation and stimulates collagen production by cultured mesangial cells. We conducted the following experiments to ascertain whether vitamin E, a lipophilic antioxidant agent, could reverse these effects in vitro. Rat mesangial cells were grown to confluence and then maintained for 7 additional days in control media (DME) containing 5.6 mM glucose or experimental media containing 33.3 mM glucose. The test condition resulted in a near doubling of mesangial cell lipid peroxidation, assessed by measuring the content of conjugated dienes. High-glucose media also enhanced collagen production by 28% above the basal level in control media. Addition of vitamin E (100 microM) reversed both effects of the elevated ambient glucose level and prevented lipid peroxidation and normalized collagen production in cultured mesangial cells. These findings suggest that vitamin E functions as an endogenous antioxidant agent in the kidney to limit the development of glomerulosclerosis in diabetic nephropathy.
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PMID:Vitamin E prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. 802 21

The possible involvement of basement membrane-associated collagen (recognized by the monoclonal antibody JK-132) in the evolution of diabetic nephropathy was studied in kidney specimens from seven patients with noninsulin-dependent diabetes mellitus, and its distribution was compared with those of antibodies against alpha 1 to alpha 4 chains of type IV collagen. JK-132, a monoclonal antibody against basement membrane-associated collagen, reacted immunohistochemically exclusively with the mesangial matrix of the glomerular capillary. In contrast, antibodies to the alpha 1 and alpha 2 chains (IV) reacted strongly with mesangial matrix, and less strongly with the glomerular basement membrane (GBM). Antibodies to the alpha 3 and alpha 4 chains (IV) reacted mainly with GBM. In diabetes, JK-132 reacted most extensively with the expanded mesangial matrix, its staining intensity increasing with progression of the diabetic glomerulosclerosis. Antibodies to the alpha 1 and alpha 2 chains (IV) reacted prominently with the expanded mesangial matrix but less strongly with the GBM. Antibodies to the alpha 3 and alpha 4 chains reacted intensely with the thickened GBM. These results suggest that basement membrane-associated collagen differs from alpha 1 to alpha 4 chains of type IV collagen and that basement membrane-associated collagen is a good marker of mesangial expansion in diabetic nephropathy.
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PMID:Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli. 803 88


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