The Effect of Aldose Reductase Inhibition on Motor Nerve Conduction Velocity in Diabetic Rats

Yue, DK; Hanwell, Michelle A.; Satchell, Paul; Turtle, John R.

doi:10.2337/diab.31.9.789

Cited by 120 publications

(32 citation statements)

References 11 publications

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“…Another study, which used methods essentially similar to ours, revealed an even more marked reduction in sciatictibial conduction velocity than that described here. 6 We are unable to shed further light on these disagreements, but it is perhaps pertinent to stress the importance of nerve temperature measurement as part of the procedure.…”

Section: Discussionmentioning

confidence: 97%

Prevention and Reversal of Defective Axonal Transport and Motor Nerve Conduction Velocity In Rats with Experimental Diabetes by Treatment with the Aldose Reductase Inhibitor Sorbinil

1984

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This investigation was designed to determine whether the aldose reductase inhibitor Sorbinil prevented the development of or reversed defects of nerve conduction and axonal transport in streptozotocin-diabetic rats. Untreated diabetes of either 3 or 6 wk duration caused a fall in sciatic motor nerve conduction velocity (MNCV) of 6-9 m/s (P less than 0.001) and significantly reduced the accumulation of axonally transported choline acetyltransferase activity against a 24-h sciatic nerve crush. These functional defects were associated with accumulation of sorbitol and depletion of myo-inositol in the sciatic nerve. Treatment with Sorbinil (25 mg/kg/day, p.o.) throughout the period of diabetes prevented the development of all these abnormalities in both 3- and 6-wk diabetic groups. In a second study, three groups of rats were subject to 3 wk untreated diabetes followed by Sorbinil treatment (as above) for 1, 2, or 3 wk to determine whether the abnormalities expected from 3 wk of untreated diabetes could be reversed. One week of treatment significantly elevated both MNCV and choline acetyltransferase accumulation (P less than 0.05). The longer treatments progressively ameliorated these defects such that the group that received Sorbinil for the second 3 wk of a 6-wk diabetic period gave values that were similar to controls and to diabetic rats that had been given Sorbinil throughout their diabetes. Sorbitol accumulation was markedly reduced by only 1 wk of Sorbinil treatment, but the normalization of myo-inositol levels required 2 wk of treatment. These findings indicate that Sorbinil treatment in diabetic rats prevented and reversed both Sorbitol accumulation and depletion of nerve myo-inositol in the sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 97%

Prevention and Reversal of Defective Axonal Transport and Motor Nerve Conduction Velocity In Rats with Experimental Diabetes by Treatment with the Aldose Reductase Inhibitor Sorbinil

1984

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“…Aldose reductase inhibitors have been found to prevent and, in some cases, reverse abnormalities in sciatic nerve Na + -K + -ATPase activity, axonal transport, and nerve conduction velocity in experimental diabetes (27)(28)(29)(30). Although most of these studies have concentrated on somatic myelinated nerves, a few studies have suggested that there is an effect on biochemical (45), pathophysiological, and structural histopathology (14) involving the autonomic nervous system as well.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have established the participation of the sorbitol and myo-inositol pathways in the development of some of the complications of experimental diabetes (27)(28)(29)(30). Aldose reductase inhibitors have been found to prevent and, in some cases, reverse abnormalities in sciatic nerve Na + -K + -ATPase activity, axonal transport, and nerve conduction velocity in experimental diabetes (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

“…Role of polyol pathway in increased TOH activity in diabetic CG. Recent work has suggested the beneficial effect of aldose reductase inhibitors on numerous complications of diabetes, particularly in experimental animal models (27)(28)(29)(30). Institution of aldose reductase therapy with sorbinil within a day of onset of diabetes did not significantly alter the severity of diabetes as monitored by glycosylated hemoglobin values and plasma glucose ( Table 6).…”

Section: Monthsmentioning

confidence: 99%

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Tyrosine Hydroxylase Activity in Sympathetic Nervous System of Rats With Streptozocin-Induced Diabetes

Schmidt

Cogswell²

1989

Diabetes

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The activity of tyrosine hydroxylase (TOH), the rate-limiting enzyme in norepinephrine biosynthesis, was measured in selected sympathetic ganglia to develop a quantitative measure of sympathetic autonomic neuropathy in streptozocin-induced diabetic rats. Surprisingly, TOH activity was elevated twofold in diabetic prevertebral ganglia innervating the alimentary tract (i.e., superior mesenteric, celiac, and inferior mesenteric), which has terminal processes that develop neuroaxonal dystrophy in this model system. TOH activity of paravertebral ganglia (i.e., superior cervical and stellate) with nonalimentary targets was not increased in the same animals. Increased TOH activity in the prevertebral ganglia 1) developed within the 1st wk of diabetes and persisted for 10 mo, 2) did not represent a change in TOH affinity for d-1,6-methyl-5,6,7,8- tetrahydropterine cofactor, 3) was prevented by both nicotinamide pretreatment and early institution of insulin therapy, and 4) did not develop as a result of classical transsynaptic induction. Pair-feeding experiments confirmed that the most likely cause of increased TOH activity in this system was the marked hypertrophy and hyperplasia of the diabetic bowel resulting from compensatory hyperphagia. We conclude that TOH activity does not represent a suitable marker for sympathetic autonomic neuropathy in this experimental system. Rather, the increase appears to be an example of a selective increase in the synthesis of neurotransmitter enzymes, possibly in response to increased trophic support provided by the expanded target, i.e., the hypertrophic gut. The additional synthetic stress imposed on prevertebral neurons by the expansion of the innervation of the alimentary target coupled with the complex diabetic metabolic milieu may contribute to the development and selective distribution of dystrophic axonopathy to the innervation of the alimentary tract.

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“…In a number of studies, aldose reductase inhibitors (ARI) prevented development of nerve conduction or ultrastructural abnormalities associated with experimental diabetes [122,123,124]. In a one-year clinical trial, a high dose of the ARI, tolrestat, was associated with improved nerve conduction velocities (NCV), but not painful neuropathic symptoms [125].…”

Section: Investigational Therapiesmentioning

confidence: 99%

Impact of Diabetes on Vasculature: Focus on Nervous System

Skljarevski

Veves²

2005

CDR

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Chronic complications of diabetes mellitus represent a major cause of morbidity and mortality among those affected and have an enormous impact on society as a whole. Although these complications manifest as a number of clinically distinct syndromes, the pathology underlying them may be very similar, if not identical. Endothelial dysfunction leading to microcirculatory insufficiency and functional ischemia of tissues are proposed to play a pivotal role in the process of their development and progression. Diabetic complications affecting the nervous system occur not infrequently and may have disastrous consequences. This article reviews diabetic complications affecting central and peripheral nervous systems, focusing on similarities in their underlying microvascular pathology and discussing aspects of potentially successful therapeutic interventions. In addition, the article draws a parallel between microvascular dysfunction observed in persons with overt diabetes and those at risk for it.

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The Effect of Aldose Reductase Inhibition on Motor Nerve Conduction Velocity in Diabetic Rats

Cited by 120 publications

References 11 publications

Prevention and Reversal of Defective Axonal Transport and Motor Nerve Conduction Velocity In Rats with Experimental Diabetes by Treatment with the Aldose Reductase Inhibitor Sorbinil

Prevention and Reversal of Defective Axonal Transport and Motor Nerve Conduction Velocity In Rats with Experimental Diabetes by Treatment with the Aldose Reductase Inhibitor Sorbinil

Tyrosine Hydroxylase Activity in Sympathetic Nervous System of Rats With Streptozocin-Induced Diabetes

Impact of Diabetes on Vasculature: Focus on Nervous System

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