Summary
This study measured the ouabain-sensitive and ouabain-resistant adenosine triphosphatase activity in homogenates of the sciatic nerves and of pooled fourth and fifth lumbar dorsal root ganglia from rats fed 20% galactose or made diabetic with streptozotocin for either 4 or 8 weeks. Diabetes caused reductions in both fractions of sciatic nerve adenosine triphosphatase activity. After 8 weeks the ouabainsensitive fraction was 54% of control (p<0.05) and the ouabain-resistant fraction was 57% of control (p<0.05). Galactose feeding more than doubled the ouabain-sensitive adenosine triphosphatase activity in the sciatic nerve (225% of control after 4 weeks, 215% of control after 8 weeks of galactose feeding, bothp<0.01) and produced a progressive increase in the ouabain-resistant fraction (119% of control at 4 weeks (p<0.05) and 176% of control at 8 weeks (p<0.01)). In a group of rats fed galactose for 5 days, sciatic nerve ouabain-sensitive adenosine triphosphatase activity was 165% of control. Treatment with the aldose-reductase inhibitors tolrestat, ponalrestat or sorbinil prevented accumulation of polyol and depletion of myo-inositol in the sciatic nerves, indicating effective inhibition of aldose reductase. These drugs prevented completely the effect of galactose on the sciatic nerve adenosine triphosphatase activity, but had no significant effect on the reduction in adenosine triphosphatase activity in the sciatic nerves of diabetic rats. In the dorsal root ganglia galactose feeding had no measurable effect on the adenosine triphosphatase activity. Diabetes caused a modest numerical reduction in the ouabain-sensitive activity only. The findings indicate markedly different effects of diabetes and galactosaemia on the adenosine triphosphatase activity in rat sciatic nerve and show that the reduction in activity seen in the nerves of diabetic rats was not related to exaggerated polyol pathway flux.
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Willars GB, Lambourne JE, Tomlinson DR (1988) Does galactose feeding provide a valid model of exaggerated polyol-path-way flux in peripheral nerve in experimental diabetes? Diabetes 36: 1425–1431
Lambourne JE, Tomlinson DR, Brown AM, Willars GB (1987) Opposite effects of diabetes and galactosaemia on ATPase activity in rat nervous tissue. Diabetologia 30: 360–362
Das PK, Bray GM, Aguayo AJ, Rasminsky M (1976) Diminished ouabain-sensitive, sodium-potassium ATPase activity in sciatic nerves of rats with streptozotocin-induced diabetes. Exp Neurol 53: 285–288
Greene DA, Lattimer S, Ulbrecht J, Carroll P (1985) Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 8: 290–299
Greene DA, Lattimer SA (1984) Action of sorbinil in diabetic peripheral nerve: relationship of polyol (sorbitol) pathway inhibition to a myo-inositol-mediated defect in sodium-potassium ATPase activity. Diabetes 33: 712–716
Mayer JH, Tomlinson DR (1983) Prevention of defects of axonal transport and nerve conduction velocity by oral administration ofmyo-inositol or an aldose reductase inhibitor in streptozotocindiabetic rats. Diabetologia 25: 433–438
Willars GB, Calcutt NA, Tomlinson DR (1987) Impaired axonal transport of phosphofructokinase in streptozotocin-diabetic rats; effects of insulin and the aldose reductase inhibitor, ‘ponalrestat’. Diabetologia 30: 239–243
Greene DA, Yagihashi S, Lattimer SA, Sima AAF (1984) Nerve Na+-K+-ATPase, conduction, and myo-inositol in the insulin- deficient BB rat. Am J Physiol 247: E534–E539
Greene DA, Chakrabarti S, Lattimer SA, Sima AAF (1987) Role of sorbitol accumulation and myo-inositol depletion in parano- dal swelling of large myelinated fibers in the insulin-deficient spontaneously diabetic Bio-breeding rat. J Clin Invest 79: 1479–1485
Calcutt NA, Tomlinson DR, Willars GB (1988) Ganglioside treatment of diabetic rats; effects on nerve adenosine triphosphatase activity and motor nerve conduction velocity. Life Sci 42: 1515–1520
Greene DA, Lattimer SA (1983) Impaired rat sciatic nerve sodium-potassium ATPase in acute streptozotocin diabetes and its correction by dietary myo-inositol supplementation. J Clin Invest 72: 1058–1063
Lambourne JE (1988) Neurological defects in galactose-fed rats. PhD Thesis, University of Nottingham, pp 69–70
Llewelyn JG, Thomas PK (1987) Perineurial sodium-potassium- ATPase activity in streptozotocin-diabetic rats. Exp Neurol 97: 375–382
Llewelyn JG, Patel NJ, Thomas PK, Stribling D (1987) Sodium, potassium adenosine triphosphatase activity in peripheral nerve tissue of galactosaemic rats. Effect of aldose reductase inhibition. Diabetologia 30: 971–972
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Lambourne, J.E., Brown, A.M., Calcutt, N. et al. Adenosine triphosphatase in nerves and ganglia of rats with streptozotocin-induced diabetes or galactosaemia; effects of aldose reductase inhibition. Diabetologia 31, 379–384 (1988). https://doi.org/10.1007/BF02341507
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DOI: https://doi.org/10.1007/BF02341507