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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out.
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PMID:[Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. 1 65

Oral administration of quercitrin, an inhibitor of aldose reductase, leads to a significant decrease in the accumulation of sorbitol in the lens of diabetic Octodon degus. The onset of cataract is effectively delayed when quercitrin is continuously administered. Thus in these diabetic animals, as in galactosemic rats, the use of an effective aldose reductase inhibitor impedes the course of cataract development. These observations support the hypothesis that in diabetes, as in galactosemia, aldose reductase plays a key role in initiating the formation of lens opacity.
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PMID:Diabetic cataracts and flavonoids. 40 44

The effects of glycation of either albumin, a plasma protein, or GBM were examined in an in vitro model of GBM permeability. Albumin was incubated with glucose in vitro, and nonglycated and glycated albumin were separated by affinity chromatography. Rat GBM was glycated either in vivo after the induction of diabetes or in vitro after incubation with 25 mM glucose. 150 micrograms of GBM was consolidated in an ultrafiltration cell, and albumin permeability across the GBM filter was assessed at an applied pressure (50 mmHg) selected to approximate glomerular capillary pressure in vivo. The sieving coefficient of glycated albumin was greater than the sieving coefficient of nonglycated albumin (0.25 +/- 0.03 vs. 0.10 +/- 0.02; P < 0.05). GBM glycated in vivo in diabetic rats exhibited native albumin and water permeability that was indistinguishable from that for GBM from control rats. Similarly, GBM glycated in vitro by incubation with 25 mM glucose exhibited water and albumin permeability identical to that for GBM incubated in buffer. Thus, the glycation of albumin, but not of GBM, leads to enhanced permeability in an in vitro GBM filtration system. Increased permeability of glycated albumin may contribute to albuminuria and/or renal injury in states of increased circulating glycated albumin such as diabetes and experimental galactosemia.
Diabetes 1992 Nov
PMID:Glycation of albumin, not glomerular basement membrane, alters permeability in an in vitro model. 139 17

Enzymatically mediated crosslinks and nonenzymatic glycation were quantified in granulation tissue collagen in two models of hyperglycemia, diabetes and galactosemia, that have opposite effects on collagen solubility. The effects of castration, which alters collagen solubility, was also investigated. Collagen from both diabetic and galactosemic rats had significantly increased levels of dihydroxylysinonorleucine (DHLNL), a difunctional reducible crosslink. Galactosemic rats had significantly decreased levels of hydroxypyridinium, a trifunctional product of DHLNL and hydroxylysine, relative to control values, while diabetic rats had normal levels. Values for all other detectable crosslinks in collagen from hyperglycemic rats were indistinguishable from control values. Nonenzymatic glycation was increased in both groups of hyperglycemic rats. In diabetic rats, but not in galactosemic rats, nonenzymatic glycation was strongly correlated with DHLNL content. Castration had no effect on crosslink content of collagen from diabetic or galactosemic rats. This study demonstrates that (1) collagen crosslinking is abnormal in granulation tissue collagen in both experimental diabetes and galactosemia, (2) these changes are similar to those observed in skin collagen from insulin-dependent diabetic subjects and (3) the crosslinking abnormalities are not correlated with alterations in collagen solubility. We conclude that hyperglycemia-associated increases in immature crosslinks cannot account for altered collagen solubility, although impaired maturation of such crosslinks may be partially responsible for the lathyrogenic effect of galactosemia.
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PMID:Lysyl oxidase-mediated crosslinking in granulation tissue collagen in two models of hyperglycemia. 167 90

Effects of sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus age-matched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by sorbinil. The fractional volume of the glomerulus occupied by mesangium (Vvmes) was increased in diabetic and galactose fed rats versus age-matched controls, and was unaffected by sorbinil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Discordant effects of the aldose reductase inhibitor, sorbinil, on vascular structure and function in chronically diabetic and galactosemic rats. 177 18

To examine the association between renal hemodynamic abnormalities and the development of diabetic kidney disease, glomerular filtration rate (GFR) and renal plasma flow (RPF) have been determined in dogs with alloxan-induced diabetes or experimental galactosemia of 1 to 5 years duration. GFR and RPF were significantly greater than normal in insulin-deficient diabetic dogs. GFR was also significantly greater than normal in the galactosemic animals, and RPF tended to be elevated even though GFR and RPF were measured at time of day when plasma galactose is no longer elevated. GFR and effective RPF (eRPF) were found to increase in normal animals upon acute elevation of blood galactose or glucose concentration. Thus, GFR is supranormal in experimental galactosemia, as well as in diabetes, although galactosemia has been shown not to cause nephromegaly, mesangial expansion, or glomerular obliteration, which are typical of diabetes. Administration of an aldose reductase inhibitor (Sorbinil) at dosages sufficient to significantly reduce erythrocyte polyol concentration did not significantly influence GFR or RPF in diabetic or galactosemic dogs.
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PMID:Renal hemodynamics in experimentally galactosemic dogs and diabetic dogs. 190 44

Chronic experimental hyperglycemia mediated by galactose has been shown to induce browning and cross-linking of rat tail tendon collagen that could be duplicated in vitro by nonenzymatic galactosylation. To investigate the nature of these changes, Sprague-Dawley rats were placed on a 33% galactose diet without and with sorbinil for 6 and 12 mo. Collagen-linked fluorescence and pentosidine cross-links increased with age and galactosemia in tail tendons (P less than 0.001) and skin but were essentially unresponsive to aldose reductase inhibition (ARI). In contrast, tendon breaking time in urea, a likely parameter of cross-linking, was markedly improved (P less than 0.001) by ARI. Fluorescence that was inhibited by sorbinil treatment was increased in pepsin and proteinase K digest of aortic tissue from galactosemic rats (P less than 0.001), but impaired enzymatic digestibility was not observed. Systolic blood pressure as potential consequence of aortic stiffening was not increased in galactosemia. These data suggest that fluorescence in skin and tendon might be in part due to advanced glycosylation and pentosidine formation because these were not decreased by ARI. However, they also suggest that nonfluorescent cross-links may also be forming because, in contrast to fluorescence, tail tendon breaking time was partly corrected by ARI. Thus, it appears that extracellular matrix changes in chronic galactosemia are complex, being partly attributable to advanced glycosylation and partly to polyol-pathway activation.
Diabetes 1991 Aug
PMID:Tissue-specific effects of aldose reductase inhibition on fluorescence and cross-linking of extracellular matrix in chronic galactosemia. Relationship to pentosidine cross-links. 190 47

Experimental galactosemia, induced by feeding rats a galactose enriched diet, reproduces many of the neural and ocular complications of diabetes and induces protein glycation and polyol accumulation. To explore the role of these biochemical abnormalities in the pathogenesis of glomerular injury, adult male Sprague-Dawley rats were placed on either a 50% galactose or 50% glucose diet. After two months, galactose fed rats exhibited elevated excretory rates of protein, albumin, and IgG. Blebbing and ballooning of the glomerular epithelial cells were apparent in rats on the galactose supplemented diet. Morphometric evaluation of the glomeruli revealed an increase in the fractional and absolute volume of the glomerular epithelial cells, but glomerular and mesangial volume, basement membrane thickness, and epithelial foot process width were similar on the two diets. Glycation of the glomerular basement membrane was increased in the galactose fed rats. Glomerular micropuncture revealed similar glomerular pressures and flow rates on the two diets. Aldose reductase inhibition had no effect on galactose induced proteinuria. These results suggest that biochemical abnormalities such as protein glycation may be important in the pathogenesis of altered glomerular permselectivity in diabetic nephropathy.
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PMID:Functional and structural alterations of the glomerular permeability barrier in experimental galactosemia. 191 Jan 23

Recent evidence obtained from both galactosemic dogs and rats indicated that aldose reductase inhibitors could prevent several capillary lesions which were similar to those typical of diabetic retinopathy in humans. The present study demonstrates that diabetes-like histopathological changes in the intact retina, which were not visible in the vessel whole mounts used previously, can also be prevented. Sprague-Dawley rats were fed diets containing 50% galactose with or without an aldose reductase inhibitor (tolrestat). After 28 months of galactose feeding, the findings from retinal transections examined by light and electron microscopy were consistent with reports on vessel whole mounts, but showed several additional changes. There was a marked increase in the thickness of the retinal inner limiting membrane, as well as in the capillary basement membranes. There was extensive gliosis and disruption of retinal layers as well as pericyte degeneration, endothelial cell proliferation, accellularity, capillary dilation, and microaneurysm formation. The contents of pericyte compartments in the capillary wall were often replaced with non-pericyte cytoplasm, which appeared glial cell-like. Many of the lumens of acellular capillaries were occluded with debris from degenerating endothelial cells or with cytoplasm possibly originating from glial cell processes. Structures suggestive of degenerated microaneurysms were present mainly in the inner nuclear and outer plexiform layers. The microaneurysms and other major changes were limited to the central and paracentral retina. All these retinal lesions were prevented with orally administered tolrestat. Thus, long-term galactosemia in rats induced histopathologically visible angiopathies, simulating those occurring in background diabetic retinopathy in humans, and these were prevented by treatment with an aldose reductase inhibitor.
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PMID:Diabetes-related histopathologies of the rat retina prevented with an aldose reductase inhibitor. 211 Sep 7

Breakdown of the blood-retinal barrier (BRB) is an early event in diabetic and galactosemic rats, but the location and nature of the specific defect(s) are controversial. Using an electron microscopic immunocytochemical technique, the retinas of normal, diabetic, and galactosemic rats were immunostained for endogenous albumin. Normal rats showed little evidence of BRB breakdown at either the inner barrier (retinal vasculature) or the outer barrier (retinal pigment epithelium) (RPE). In diabetic and galactosemic rats, as was true in human diabetics, BRB breakdown occurred predominantly at the inner BRB, but in some cases at the outer barrier as well. Treatment with the aldose reductase inhibitor sorbinil largely prevented BRB failure in galactosemic rats. In the inner retina of diabetic and galactosemic rats, albumin was frequently demonstrated on the abluminal side of the retinal capillary endothelium (RCE) in intercellular spaces, basal laminae, pericytes, ganglion cells, astrocytes, and the perinuclear cytoplasm of cells in the inner nuclear layer. Albumin did not appear to cross RCE cell junctions; however, it was occasionally seen in RCE cytoplasm of galactosemic rats. In the outer retina, albumin was frequently detected in the subretinal space, in the intercellular space between photoreceptors, and in the perinuclear cytoplasm of photoreceptor cells, but was only infrequently found in the RPE cells constituting the barrier. Albumin derived from the choroidal vasculature did not appear to cross the tight junctions of the RPE. These findings suggest that specific sites of BRB compromise are infrequent but that once albumin has crossed the RCE or RPE it freely permeates the retinal tissue by filling intercellular spaces and permeating the membranes of cells not implicated in BRB formation. The diffuse cytoplasmic staining of some RCE and RPE cells suggests that the predominant means of BRB breakdown in diabetes and galactosemia involves increased focal permeability of the surface membranes of the RCE and RPE cells rather than defective tight junctions or vesicular transport.
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PMID:Ultrastructural localization of blood-retinal barrier breakdown in diabetic and galactosemic rats. 211 24


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