Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235

Yasuda, Hitoshi; Sonobe, Masanobu; Yamashita, M.; Terada, Masahiko; Hatanaka, I.; Huitian, Z.; Shigeta, Yukio

doi:10.2337/diabetes.38.7.832

Cited by 75 publications

(29 citation statements)

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“…For the former, this agrees with previously reported measurements over a 4-h period [44]. The deficit in laser-Doppler flux with diabetes also agrees with several reports [6,8,43,[45][46][47][48]. It was further suggested that reduced blood flow in diabetic rats is only found when they are ketotic [49].…”

Section: Methodssupporting

confidence: 81%

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

et al. 1997

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Elevated polyol pathway activity has been implicated in the development of diabetic complications, including neuropathy [1]. In diabetic models, inhibitors of the first enzyme in the pathway, aldose reductase, prevent or correct nerve conduction velocity (NCV) and regeneration deficits [2][3][4][5][6][7][8][9][10][11][12][13]. Clinical trials of aldose reductase inhibitors (ARIs) have shown modest improvements in neurological symptoms, NCV, sensory measures, and an increase in nerve fibre regeneration [14-17] despite a less effective polyol pathway blockade than was found necessary for functional effects in animal studies [6,10,18].Several hypotheses have been advanced to explain the action of ARI. Some putative mechanisms are primarily dependent on the first half of the polyol pathway, conversion of glucose to sorbitol by aldose Diabetologia (1997) 40: 271-281 Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats Summary Aldose reductase inhibitors (ARIs) attenuate diabetic complications in several tissues, including lens, retina, kidney, blood vessels, striated muscle and peripheral nerve. However, it is unclear whether their action in diabetes mellitus depends directly on inhibiting the conversion of glucose to sorbitol by aldose reductase or indirectly by reducing the sorbitol available for subsequent metabolism to fructose by sorbitol dehydrogenase. To identify the polyol pathway step most relevant to complications, particularly neuropathy, we compared the biochemical effects of a sorbitol dehydrogenase inhibitor, WAY-135 706, (250 mg ⋅ kg −1 ⋅ day −1 ) and an ARI, WAY-121 509, (10 mg ⋅ kg −1 ⋅ day −1 ) on a variety of tissues, and their effects on nerve perfusion and conduction velocity. After 6 weeks of untreated streptozotocin diabetes, rats were treated for 2 weeks. Sorbitol was elevated 2.1-32.6-fold by diabetes in lens, retina, kidney, aorta, diaphragm, erythrocytes and sciatic nerve; this was further increased (1.6-8.2-fold) by WAY-135 706 whereas WAY-121 509 caused a marked reduction. Fructose 1.6-8.0-fold elevated by diabetes in tissues other than diaphragm, was reduced by WAY-135 706 and WAY-121 509, except in the kidney. Motor and sensory nerve conduction velocities were decreased by 20.2 and 13.9 %, respectively with diabetes. These deficits were corrected by WAY-121 509, but WAY-135 706 was completely ineffective. A 48.6 % diabetes-induced deficit in sciatic nutritive endoneurial blood flow was corrected by WAY-121 509, but was unaltered by WAY-135 706. Thus, despite profound sorbitol dehydrogenase inhibition, WAY-135 706 had no beneficial effect on nerve function. The data demonstrate that aldose reductase activity, the first step in the polyol pathway, makes a markedly greater contribution to the aetiology of diabetic neurovascular and neurological dysfunction than does the second step involving sorbitol dehydrogenase. [Diabetologia (1997) 40: ...

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Section: Methodssupporting

confidence: 81%

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

et al. 1997

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“…The deficit of approximately 50% in nerve laser Doppler flux in diabetic rats is consistent with results from other research groups who have either used Doppler flowmetry (Yasuda et al, 1989;Maxfield et al, 1993;Kappelle et al, 1993;Cameron et al, 1994b) or other methods Monafo et al, 1988;Cameron et al, 1991;Hotta et al, 1992) to estimate nerve perfusion in experimental diabetes. The validity of Doppler flowmetry as an index of nerve blood flow requires comment and, in the aforementioned papers (Stevens et al, 1993b;, we discussed the limitations and fidelity of the technique.…”

Section: Acute Bosentan Administrationsupporting

confidence: 78%

“…Although the aetiology of this conduction deficit is unknown, a role for nerve ischaemia is supported by findings of nerve hypoxia in diabetic patients (Newrick et al, 1986) and animals , together with poor nerve blood flow in the latter Monafo et al, 1988;Yasuda et al, 1989;Cameron et al, 1991). Furthermore, several compounds which improve nerve conduction in experimental diabetes appear to act by attenuating nerve ischaemia (Yasuda et al, 1989;Stevens et al, 1993b;Maxfield et al, 1993;Cameron et al, 1994a). The mechanism(s) responsible for reduced nerve perfusion remain unclarified, but the disordered endothelial function associated with diabetes (Stout, 1987) may cont-ribute.…”

Section: Introductionmentioning

confidence: 81%

Effects of endothelin receptor antagonism with bosentan on peripheral nerve function in experimental diabetes

Stevens

Tomlinson

1995

British J Pharmacology

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1 The effects of the non-selective endothelin (ET) receptor (ETA/ETB) antagonist, bosentan, on sciatic nerve dysfunction in experimental diabetes were investigated. 2 Rats with 5-6 weeks untreated streptozotocin-diabetes exhibited characteristic slowed motor nerve conduction velocity (mean ± s.d., 36.6 ± 3.4 m s-') and nerve laser Doppler flux (197 ± 64 arbitrary units) compared to age-matched control animals (42.7 ± 2.4 m s-' and 398 ± 77 arbitrary units, respectively). Preventative treatment of diabetic rats with bosentan at 100 mg kg-' day-' p.o. attenuated both these deficits (39.7 ± 3.0 m s-' and 305 ± 56 arbitrary units, respectively) without affecting mean arterial pressure.3 In control and untreated diabetic rats, ET-1, 1 nmol kg-' i.v., caused an initial hypotension (duration, 30 ± 13 and 26 ± 9 s, respectively; change in mean arterial pressure, -27 ± 13 and -25 ± 7 mmHg, respectively) followed by prolonged hypertension (change in mean arterial pressure, 52 ± 18 and 31 ± 5 mmHg, respectively). Effectiveness of the chronic bosentan treatment was demonstrated by inhibition of the hypotensive response to ET-1 in treated diabetic rats (duration, 5 ± 2 s; change in mean arterial pressure, -4 + 2 mmHg) although the hypertension was unaltered (change in mean arterial pressure, 32 + 9 mmHg). 4

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“…In comparison, in peripheral nerves of diabetic rats, where blood flow is reduced by approximately 50 % [43,44], increased lactate and decreased PCr concentrations have been observed [22,45,46]. The reductions in PCr are still relatively small and have not been found consistently [47,46]. In the superior cervical ganglion, which like the brain has a higher metabolic rate, blood flow is reduced by 45 % and PCr is reduced by 38 % in STZ-diabetic rats [48,46].…”

Section: Discussionmentioning

confidence: 85%

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

et al. 2001

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It is becoming increasingly clear that the brain is another site of diabetic end-organ damage [1]. Some diabetic patients develop cognitive deficits, which are generally moderate in young adults [2] but can be more pronounced in the elderly [3]. Recent epidemiological studies even report an association between diabetes and dementia [3,4]. Given the prevalence of diabetes among the elderly and the effect of cognitive impairment and dementia on the quality of life of patients and health care resources, a better understanding of the effects of diabetes on the brain is needed.Experimentally diabetic rodents develop cerebral deficits similar to those observed in diabetic patients. Streptozotocin (STZ)-diabetic rats have been found to have impaired learning and memory functions [5] and increases in the peak latencies of brainstem audi- Diabetologia (2001) Abstract Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31 P and 1 H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.Results. In 31 P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1 H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1 H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (±14 % and ±23 %) and Nacetylaspartate:choline (±21 % and ±17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in Nacetylaspartate levels in the brain of STZ-diabetic rats were shown by 1 H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346±353]

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Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235

Cited by 75 publications

References 0 publications

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Effects of endothelin receptor antagonism with bosentan on peripheral nerve function in experimental diabetes

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

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