Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function

2002 ◽  
Vol 283 (5) ◽  
pp. E1067-E1075 ◽  
Author(s):  
Mark A. Yorek ◽  
Lawrence J. Coppey ◽  
Jill S. Gellett ◽  
Eric P. Davidson ◽  
Xinyu Bing ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Atpase Activity ◽  
Motor Nerve ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Neural Function ◽  
Adrenal Androgen ◽  
Dhea Treatment ◽  
Neural Dysfunction

Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes-induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin-induced diabetic rats with 0.1, 0.25, or 0.5% DHEA caused a concentration-dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment, which are decreased in diabetes. At 0.25%, DHEA significantly prevented the diabetes-induced increase in serum thiobarbituric acid-reactive substances and sciatic nerve conjugated diene levels. This treatment also reduced the production of superoxide by epineurial arterioles of the sciatic nerve. DHEA treatment (0.25%) significantly improved vascular relaxation mediated by acetylcholine in epineurial vessels of diabetic rats. Sciatic nerve Na+-K+-ATPase activity and myoinositol content was also improved by DHEA treatment, whereas sorbitol and fructose content remained elevated. These studies suggest that DHEA, by preventing oxidative stress and perhaps improving sciatic nerve Na+-K+-ATPase activity, may improve vascular and neural dysfunction in diabetes.

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats

2005 ◽  
Vol 289 (1) ◽  
pp. E113-E122 ◽  
Author(s):  
Christine L. Oltman ◽  
Lawrence J. Coppey ◽  
Jill S. Gellett ◽  
Eric P. Davidson ◽  
Donald D. Lund ◽  
...  
Keyword(s):  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Zucker Rats ◽  
Vascular Relaxation ◽  
Calcitonin Gene ◽  
Markers Of Oxidative Stress ◽  
Endoneurial Blood Flow ◽  
Zdf Rats ◽  
Neural Dysfunction

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12–14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8–10 wk of age in ZDF diabetic rats and after ∼16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia.

Reduction of cyclic AMP in the sciatic nerve of rats made diabetic with streptozotocin and the mechanism involved

1993 ◽  
Vol 136 (3) ◽  
pp. 431-438 ◽  
Author(s):  
H. Shindo ◽  
M. Tawata ◽  
T. Onaya
Keyword(s):  
Sciatic Nerve ◽  
Cyclic Amp ◽  
Nerve Conduction Velocity ◽  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Nerve Function ◽  
Camp Content ◽  
Motor Nerve Conduction ◽  
Sciatic Nerves

ABSTRACT We have investigated the relationship between cyclic nucleotides and nerve function in the sciatic nerve of rats made diabetic with streptozotocin. Cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly (P < 0·05) lower than in those of normal rats, while cyclic GMP content did not differ between the two groups. Administration of the stable prostacyclin analogue iloprost or dibutyryl cyclic AMP (dbcAMP) significantly (P<0·05) restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. There was a positive correlation between cAMP content in the sciatic nerves and motor nerve conduction velocity in both normal and diabetic rats. Endoneurial preparations of sciatic nerves obtained from normal rats were incubated in Krebs–Ringer bicarbonate buffer containing d-glucose (30 or 5·5 mmol/l). Cyclic AMP accumulation was significantly (P<0·05) suppressed in the buffer containing 30 mmol d-glucose/l compared with that containing 5·5 mmol/l. Iloprost (P<0·05) and dbcAMP (P<0·01) increased cAMP accumulations in the tissues incubated in buffer containing both 5·5 and 30 mmol d-glucose/l. When non-metabolizing hexoses, such as l-glucose or 3-O-methylglucose instead of d-glucose were used, cAMP accumulations at 30 mmol hexose/1 were not significantly different from those at 5·5 mmol/l. Cyclic AMP phosphodiesterase activity in the sciatic nerves of diabetic rats did not change compared with that in nerves from normal rats. Although not significant, mean ATP content in the sciatic nerves of diabetic rats was about 30% lower than that in nerves of normal rats. Basal, iloprost-stimulated and forskolin-stimulated adenylate cyclase activities in the sciatic nerves of diabetic rats were significantly (P<0·05) reduced when compared with those of control rats. We therefore conclude that reduction of cAMP content in peripheral nerves may be involved in the pathogenesis of diabetic neuropathy and is mainly caused by the impairment of adenylate cyclase activity in the diabetic state. Journal of Endocrinology (1993) 136, 431–438

scholarly journals Effect of Treating Streptozotocin-Induced Diabetic Rats With Sorbinil, Myo-Inositol or Aminoguanidine on Endoneurial Blood Flow, Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

2002 ◽  
Vol 3 (1) ◽  
pp. 21-36 ◽  
Author(s):  
Lawrence J. Coppey ◽  
Jill S. Gellett ◽  
Eric P. Davidson ◽  
Joyce A. Dunlap ◽  
Mark A. Yorek
Keyword(s):  
Blood Flow ◽  
Sciatic Nerve ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Nerve Conduction Velocity ◽  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Motor Nerve Conduction ◽  
Endoneurial Blood Flow

Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of motor nerve conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve motor nerve conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on motor nerve conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and motor nerve conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

scholarly journals Effect of Fidarestat andα-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction

2004 ◽  
Vol 5 (2) ◽  
pp. 123-135 ◽  
Author(s):  
M. A. Yorek ◽  
L. J. Coppey ◽  
J. S. Gellett ◽  
E. P. Davidson ◽  
D. D. Lund
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Lipoic Acid ◽  
Vascular Dysfunction ◽  
Motor Nerve ◽  
Diabetic Rats ◽  
Motor Nerve Conduction Velocity ◽  
Dihydrolipoic Acid ◽  
Higher Doses ◽  
Neural Dysfunction

In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination ofα-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy ofα-lipoic acid as monotherapy toward preventing diabetic vascular and neural dysfunction.Treating diabetic rats with the combination of 0.25%α-lipoic acid (in the diet) and fidarestat (3 mg/kg body weight) prevented the diabetesinduced slowing of motor nerve conduction velocity and endoneurial blood flow. This therapy also significantly improved acetylcholine-mediated vasodilation in epineurial arterioles of the sciatic nerve compared to nontreated diabetic rats. Treating diabetic rats with 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) was equally or more effective in preventing vascular and neural dysfunction than was monotherapy of diabetic rats with higher doses ofα-lipoic acid or fidarestat. Treating diabetic rats with the combination of 0.25%α-lipoic acid and fidarestat (3 mg/kg body weight) significantly improved several markers of oxidative stress and increased the serum levels of bothα-lipoic acid and dihydrolipoic acid. These studies suggest that combination therapy consisting ofα-lipoic acid and fidarestat may be more efficacious in preventing diabetes-induced vascular and neural dysfunction in peripheral tissue compared to monotherapy, which requires higher doses to be equally effective. The effect of this combination therapy may in part be due to the increased production and/or level of dihydrolipoic acid.

Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats

1996 ◽  
Vol 134 (4) ◽  
pp. 467-473 ◽  
Author(s):  
Yosuke Miyauchi ◽  
Hisataka Shikama ◽  
Toshiyuki Takasu ◽  
Hideaki Okamiya ◽  
Masako Umeda ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Atpase Activity ◽  
Nerve Conduction ◽  
Renal Cortex ◽  
Motor Nerve ◽  
Diabetic Rats ◽  
Myelinated Fiber ◽  
Peripheral Tissues ◽  
Motor Nerve Conduction ◽  
Peripheral Motor

Miyauchi Y, Shikama H, Takasu T, Okamiya H, Umeda M, Hirasaki E, Ohhata I, Nakayama H, Nakagawa S. Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats. Eur J Endocrinol 1996:134:467–73. ISSN 0804–4643 The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K+-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K+-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy. Hisataka Shikama, Endocrinology and Metabolic Disease Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305 Japan

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