Glomerular polyol accumulation in diabetes and its prevention by oral sorbinil

Beyer‐Mears, A.; Ku, L.; Cohen, Morrel H.

doi:10.2337/diabetes.33.6.604

Cited by 89 publications

(35 citation statements)

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“…Cellular rayo-inositol depletion has been discussed as a pathogenetic mechanism in diabetic neuropathy (2) and nephropathy (5). The lack of significant changes in the present study does not accord with this concept, but confirms recent findings of Loy et al (28).…”

Section: Trimethylaminessupporting

confidence: 80%

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Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Schmolke

Schleicher²,

Guder³

1992

Clinical Chemistry and Laboratory Medicine

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Summary:The polyols, sorbitol and wyo-inositol, seem to be involved in the development of diabetic complications of different organs. High concentrations of both polyols were found in kidney medulla in addition to trimethylamines. To investigate the influence of diabetes mellitus on the regulation of both polyols and glycerophosphorylcholine in kidney, these osmolytes were quantitated enzymatically along the corticopapillary axis in untreated, streptozotocin-diabetic and insulin-treated streptozotocin-diabetic rats.In control animals three individual osmolyte patterns were found: a steep gradient of sorbitol in the papilla, increasing amounts of glycerophosphorylcholine from the outer medulla to the papilla, and nearly equal amounts of wyo-inositol in the renal medulla, decreasing towards the cortex.Diabetic rats exhibit an up to fourfold increase of inner medullary sorbitol, whereas myo-inositol was only elevated in the outer medulla. Glycerophosphorylcholine was lowered in the papillary tip and elevated in the outer medulla and cortex.

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Section: Trimethylaminessupporting

confidence: 80%

“…to be involved in the pathomechanisms of diabetic Beyer-Mears et al found a sorbitol accumulation in complications. Thus sorbitol accumulation in various glomeruli of diabetic rats, which was reversed by cells was shown to correlate with diabetic ophthal-treatment with an aldose reductase inhibitor (5). Inmopathy and neuropathy (1).…”

Section: Introductionmentioning

confidence: 99%

Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Schmolke

Schleicher²,

Guder³

1992

Clinical Chemistry and Laboratory Medicine

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“…This conclusion may in agreement with the Mizutani et al report [36] , which stated that selective Müller cell functional abnormalities in early stage of the development of diabetic retinopathy, and with the report of Dubois et al [37] , who found Müller cells death causes retinal dysplasia, photoreceptor apopotosis, and finally retinal degeneration and proliferation of the retinal pigment epithelium. Another reason that reinforce the concept of retinal degeneration by sorbitol pathway is the protection or delaying of diabetic retinopathy by using aldose reductase inhibitor (tolrestat) in diabetic rats [14] , prevention of glomerular disease by aldose reductase inhibitor (sorbinil) in diabetic rats [38] , correcting corneal endothelial changes in diabetic patient by topical aldose reductase inhibitor (placebo) in diabetic patients [39] , Prevention of diabetic complications and nerve tissue by aldose reductase inhibitors (sorbinil or sulindac) in rats lens [40] , prevention of diabetic retinopathy by aldose reductase inhibitor (sorbinil) in diabetic patients [41] , and prevention of basement membrane thickening by aldose reductase inhibitor (sorbinil) in retina of galactosemic rats [3] .…”

Section: Discussionmentioning

confidence: 97%

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

Ramadan¹

2007

American J. of Pharmacology and Toxicology

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Abstract:The present study investigated the sorbitol toxicity on the retinas of normal albino rats and founded by the light microscope that intra-peritoneal injection of Sorbitol (10-mg/kg-body weight per day) for 24 weeks produced similar diabetic like retinal lesions in these rats. The retinopathic effects of sorbitol injection affect retinal microvessels, pigment epithelium, neural retina and glial cells. Cytoplasmic vacuolation of the pigment epithelium and oedema of the neural retinal cells were evident. Microvascular abnormalities include thick-walled, elongated and dilated blood capillaries. The abnormal capillaries showed aneurysms and were occluded with deformed, fragmented, and adherent blood cells. Another finding was the pyknosis of glial cells. The present investigation concluded that sorbitol is toxic to the retinal tissue and it may play a role in the setup of diabetic retinopathy.

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“…Beyer-Mears et al [15] reported in 1984 that 6 weeks after the induction of diabetes the glomerular sorbitol content had increased while the myo-inositol content had decreased and that these alterations were normalized by sorbinil treatment. These findings have led to the suggestion that gtomerular hyperfiltration in diabetes may be linked to enhanced polyol pathway activity.…”

Section: Discussionmentioning

confidence: 99%

Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats

et al. 1992

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Summary. The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric garage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/1 without large day-today fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbitot accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.Key words: Streptozotocin diabetic rat, aldose reductase inhibition, glomerular filtration rate, ultrafiltration pressure, albuminuria.Glomerular hyperfiltration, intrarenal hypertension and kidney enlargement are typical findings in the early stage of human Type 1 (insulin-dependent) diabetes mellitus as well as in experimental diabetes [1][2][3][4]. It has been shown that in experimental diabetes, elevations in single nephron glomerular filtration rate (SNGFR) result from concomitant elevations in ultrafiltration pressure and glomerular plasma flow [5]. It has been suggested that these early glomerular haemodynamic abnormalities, and in particular the elevated ultrafiltration pressure, constitute the major pathogenetic factor in the progressive glomerular sclerosis that eventually develops in a substantial number of Type 1 diabetic patients [6].The mechanisms behind intrarenal hypertension and glomerular hyperfiltration in diabetes have not been fully clarified. One hypothesis suggests that disturbances in the polyol pathway induced by the increased cellular uptake of glucose via an insulin-independent transport system wilI alter the regulation of renal haemodynamics [7]. Evidence has been presented which both supports and rejects this hypothesis. Variations in the severity of diabetes and variations in diabetic control may have contributed to the inconsistencies in the results [5].Such inconsistencies in previous reports indicate the need for a study with a well-standardized experimental protocol. This need is emphasized by the fact that numerous clinical studies have recently been started to test the effects of aldose reductase inhibitors on the various complications of diabetes in humans. The present study performed on rats with streptozotocin-induced diabetes has attempted to meet the above-mentioned need. The protocols were rigorously standardized so that the rats would p...

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Glomerular polyol accumulation in diabetes and its prevention by oral sorbinil

Cited by 89 publications

References 0 publications

Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats

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