Summary
A possible relationship between increased sorbitol concentration and decreased myo-inositol concentration in peripheral nerves of diabetic rats has been examined. To this end, sorbinil, an aldose reductase inhibitor, was used either to prevent or reverse elevation of nerve sorbitol concentration in diabetic rats. Sorbinil treatment at 20 mg · kg-1 · day-1 prevented elevation of nerve sorbitol levels in early diabetes and reduced sorbitol concentration from 2.38 to 0.51 μmol/g in rats diabetic for 10 weeks. This treatment reduced the increase in nerve fructose concentration and prevented the reduced myo-inositol concentration found in diabetic rat nerve (control 3.63, diabetic 2.40, diabetic/sorbinil, 3.56 μmol/g). Sorbniil treatment did not prevent a significant slowing of motornerve conduction velocity at 10 weeks although treatment reduced the extent of slowing. Sorbinil treatment at 25 mg · kg-1 · day-1 reduced elevated sorbitol and fructose concentrations in diabetic rat nerve and normalised myo-inositol concentration. Myo-inositol treatment at 650 mg · kg-1 · day-1 did not affect the elevated concentrations of sorbitol, fructose or glucose in peripheral nerves of diabetic rats, but it did restore reduced myo-inositol concentration. Both sorbinil and myo-inositol treatment partially reversed the slowing of motor-nerve conduction velocity in diabetic rats. These results are discussed in relation to the involvement of sorbitol and myo-inositol metabolism in the aetiology of diabetic neuropathy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Eliasson SG (1964) Nerve conduction changes in experimental diabetes. J Clin Invest 43: 2353–2358
Greene DA, De Jesus PV, Winegrad AI (1975) Effects of insulin and dietary myo-inositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. J Clin Invest 55: 1326–1336
Hildebrand J, Joffroy A, Graff G, Coers C (1968) Neuromuscular changes with alloxan hyperglycemia. Arch Neurol 18: 633–641
Sharma AK, Thomas PK (1974) Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 23: 1–15
Thomas PK, Jefferys JGR, Sharma AK, Bajada S (1981) Nerve conduction velocity in experimental diabetes in the rat and rabbit. J Neurol Neurosurg Psychiatr 44: 233–238
Jakobsen J (1979) Early and preventable changes of peripheral nerve structure and function in insulin-deficient diabetic rats. J Neurol Neurosurg Psychiatr 42: 509–518
Moore SA, Peterson RG, Feiten DL, O'Connor BL (1980) A quantitative comparison of motor and sensory conduction velocities in shortand long-term streptozotocinand alloxan-diabetic rats. J Neurol Sci 48: 133–152
Bell ME, Peterson RG, Eichberg J (1982) Metabolism of phospholipids in peripheral nerve from rats with chronic streptozotocin-induced diabetes: increased turnover of phosphatidylinositol-4,5-bisphosphate. J Neurochem 39: 192–200
Brown MJ, Sumner AJ, Greene DA, Diamond SM, Asbury AK (1980) Distal neuropathy in experimental diabetes mellitus. Ann Neurol 8: 168–178
Sharma AK, Bajada S, Thomas PK (1981) Influence of streptozotocin-induced diabetes on myelinated nerve fibre maturation and on body growth in the rat. Acta Neuropathol (Berl) 53: 257–265
Yagihashi S, Kudo K, Nishihira M (1979) Peripheral nerve structures of experimental diabetes rats and the effect of insulin treatment. Tohoku J Exp Med 127: 35–44
Zemp C, Bestetti G, Rossi GL (1981) Morphological and morphometric study of peripheral nerves from rats with streptozotocininduced diabetes mellitus. Acta Neuropathol (Berl) 53: 99–106
Clements RS (1979) Diabetic neuropathy — new concepts of its etiology. Diabetes 28: 604–611
Palmano KP, Whiting PH, Hawthorne JN (1977) Free and lipid myo-inositol in tissues from rats with acute and less severe streptozotocin-induced diabetes. Biochem J 167: 229–235
Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288: 831–836
Whiting PH, Palmano KP, Hawthorne JN (1979) Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes. Biochem J 179: 549–553
Clements RS, Stockard CR (1980) Abnormal sciatic nerve myoinositol metabolism in the streptozotocin-diabetic rat. Diabetes 29: 227–235
Natarajan V, Dyck PJ, Schmid HHO (1981) Alterations of inositol lipid metabolism of rat sciatic nerve in streptozotocin-induced diabetes. J Neurochem 36: 413–419
White GL, Schellhase HU, Hawthorne JN (1974) Phosphoinositide metabolism in rat superior cervical ganglion, vagus and phrenic nerve: effects of electrical stimulation and various blocking agents. J Neurochem 22: 149–158
Gillon KRW, Hawthorne JN (1983) Sorbitol, inositol and nerve conduction in diabetes. Life Sci 32: 1943–1947
Lowry OH, Passonneau JV (1972) Preparation of tissues for analysis. In: A flexible system of enzymatic analysis. Academic Press, New York, pp 120–126
Clements RS, Morrison AD, Winegrad AI (1969) Polyol pathway in aorta: regulation by hormones. Science 166: 1007–1008
Gillon KRW, Hawthorne JN (1983) Transport of myo-inositol into endoneurial preparations of sciatic nerve from normal and streptozotocin-diabetic rats. Biochem J 210: 775–781
Greene DA, Lattimer SA (1982) Sodiumand energy-dependent uptake of myo-inositol by rabbit peripheral nerve. J Clin Invest 70: 1009–1018
Jefferys JGR, Palmano KP, Sharma AK, Thomas PK (1978) Influence of dietary myo-inositol on nerve conduction and inositol phospholipids in normal and diabetic rats. J Neurol Neurosurg Psychiatr 41: 333–339
Greene DA, Lewis RA, Lattimer SA, Brown MJ (1982) Selective effects of myo-inositol administration on sciatic and tibial motor nerve conduction parameters in the streptozotocin-diabetic rat. Diabetes 31: 573–578
Yue DK, Hanwell MA, Satchell PM, Turtle JR (1982) The effect of aldose reductase inhibition on motor nerve conduction velocity in diabetic rats. Diabetes 31: 789–794
Tomlinson DR, Holmes PR, Mayer JH (1982) Reversal, by treatment with an aldose reductase inhibitor, of impaired axonal transport and motor nerve conduction velocity in experimental diabetes mellitus. Neurosci Lett 31: 189–193
Gregersen G, Bursting H, Theil P, Servo C (1978) Myo-inositol and function of peripheral nerves in human diabetics. Acta Neurol Scandinav 58: 241–248
Clements RS, Vourganti B, Kuba T, Oh SJ, Darnell B (1979) Dietary myo-inositol intake and peripheral nerve function in diabetic neuropathy. Metabolism 28 (Suppl 1): 477–483
Salway JG, Whitehead L, Finnegan JA, Karunanayaka A, Barnett D, Payne RB (1978) Effect of myo-inositol on peripheral nerve function in diabetes. Lancet 2: 1282–1284
Gabbay KH, Spack N, Loo S, Hirsch HJ, Ackil AA (1979) Aldose reductase inhibition: studies with alrestatin. Metabolism 28 (Suppl 1): 471–476
Fagius J, Jameson S (1981) Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy — a clinical and neurophysiological study. J Neurol Neurosurg Psychiatr 44: 991–1001
Culebras A, Alio J, Herrera J-L, Lopez-Fraile MIP (1981) Effect of an aldose reductase inhibitor on diabetic peripheral neuropathy. Arch Neurol 38: 133–134
Judzewitsch RG, Jaspan JB, Polonsky KS, Weinberg CR, Halter JB, Halar E, Pfeifer MA, Vukadinovic C, Bernstein L, Schneider M, Liang K-Y, Gabbay KH, Rubenstein AH, Pone D (1983) Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med 308: 119–125
Mayhew JA, Gillon KRW, Hawthorne JN (1983) Free and lipid inositol, sorbitol and sugars in sciatic nerve obtained post-mortem from diabetic patients and control subjects. Diabetologia 24: 13–15
Ward JD (1973) The polyol pathway in the neuropathy of early diabetes. In: Camaerini-Davalos RA, Cole HS (eds) Vascular and neurological changes in early diabetes. Advances in metabolic disorders, Suppl 2. Academic Press, New York, pp 425–429
Dyck PJ, Sherman WR, Hallcher LM, Service FJ, O'Brien PC, Grina LA, Palumbo PJ, Swanson CJ (1980) Human diabetic endoneurial sorbitol, fructose and myo-inositol related to sural nerve morphometry. Ann Neurol 8: 590–596
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gillon, K.R.W., Hawthorne, J.N. & Tomlinson, D.R. Myo-inositol and sorbitol metabolism in relation to peripheral nerve function in experimental diabetes in the rat: The effect of aldose reductase inhibition. Diabetologia 25, 365–371 (1983). https://doi.org/10.1007/BF00253203
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00253203