Diabetic Neuropathy in STZ-Induced Diabetic Rat and Effect of Allogeneic Islet Cell Transplantation: Morphometric Analysis

The effect of pancreatic islet cell allotransplantation on the development of diabetic neuropathy in streptozocin-induced diabetic ACI rats was examined morphometrically with light- and electron-microscopic procedures. Peripheral nerve function was evaluated by nerve conduction velocity and evoked muscle potential amplitude measurements. Diabetes was induced at 4 mo of age, and diabetic animals were transplanted by intracerebral and intraportal grafts 2 wk later. Diabetic animals with accepted grafts returned to euglycemia and showed a normal body-weight gain over the subsequent 14-mo observation period. Transplanted animals with accepted grafts and those in whom graft rejection was induced were compared with age-matched nontransplanted diabetic rats and nondiabetic control rats at 18 mo of age. Successful allotransplantation completely prevented axonal atrophy and the characteristic nodal and paranodal structural abnormalities in diabetic nerve, as well as the typical slowing of nerve conduction velocity. Our data suggest that islet cell allotransplantation is an effective therapeutic approach to the prevention of diabetic neuropathy.

[1]  D. Greene,et al.  Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy. , 1988, The Journal of clinical investigation.

[2]  T. Brismar,et al.  Reversible and irreversible nodal dysfunction in diabetic neuropathy , 1987, Annals of neurology.

[3]  D. Greene,et al.  Role of sorbitol accumulation and myo-inositol depletion in paranodal swelling of large myelinated nerve fibers in the insulin-deficient spontaneously diabetic bio-breeding rat. Reversal by insulin replacement, an aldose reductase inhibitor, and myo-inositol. , 1987, The Journal of clinical investigation.

[4]  D. Greene,et al.  Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. , 1987, The New England journal of medicine.

[5]  P. Dyck,et al.  The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia , 1986, Annals of neurology.

[6]  P. Dyck,et al.  Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy , 1986, Annals of neurology.

[7]  S. Yagihashi,et al.  Axo-glial dysjunction. A novel structural lesion that accounts for poorly reversible slowing of nerve conduction in the spontaneously diabetic bio-breeding rat. , 1986, The Journal of clinical investigation.

[8]  D. Greene,et al.  Protein Kinase C Agonists Acutely Normalize Decreased Ouabain-inhibitable Respiration in Diabetic Rabbit Nerve: Implications for (Na,K)-ATPase Regulation and Diabetic Complications , 1986, Diabetes.

[9]  L. Autilio‐Gambetti,et al.  Experimental diabetic neuropathy: impairment of slow transport with changes in axon cross-sectional area. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Sima,et al.  Effect of endocrine pancreas allotransplantation on diabetic nerve dysfunction. , 1985, Metabolism: clinical and experimental.

[11]  T Brismar,et al.  Reversible diabetic nerve dysfunction: Structural correlates to electrophysiological abnormalities , 1985, Annals of neurology.

[12]  A. Sima.  CAN THE BB‐RAT HELP TO UNRAVEL DIABETIC NEUROPATHY? , 1985, Neuropathology and applied neurobiology.

[13]  J. Ulbrecht,et al.  Glucose-induced Alterations in Nerve Metabolism: Current Perspective on the Pathogenesis of Diabetic Neuropathy and Future Directions for Research and Therapy , 1985, Diabetes Care.

[14]  P. Thomas,et al.  The effect of insulin treatment on myelinated nerve fibre maturation and integrity and on body growth in streptozotocin-diabetic rats , 1985, Journal of the Neurological Sciences.

[15]  S. Yagihashi,et al.  Nerve Na+-K+-ATPase, conduction, and myo-inositol in the insulin-deficient BB rat. , 1984, The American journal of physiology.

[16]  J. Tai,et al.  INTRACEREBRAL ALLOTRANSPLANTATION OF PURIFIED PANCREATIC ENDOCRINE CELLS AND PANCREATIC ISLETS IN DIABETIC RATS , 1984, Transplantation.

[17]  D. Greene,et al.  Action of Sorbinil in Diabetic Peripheral Nerve: Relationship of Polyol (Sorbitol) Pathway Inhibition to a myo-Inositol-mediated Defect in Sodium-Potassium ATPase Activity , 1984, Diabetes.

[18]  D. Tomlinson,et al.  Defects of axonal transport in diabetes mellitus--a possible contribution to the aetiology of diabetic neuropathy. , 1984, Journal of autonomic pharmacology.

[19]  J. Tai,et al.  Successful Intracerebral Allotransplantation of Purified Pancreatic Endocrine Cells in Diabetic Rat , 1983, Diabetes.

[20]  D. Finegold,et al.  Polyol Pathway Activity and Myo-Inositol Metabolism: A Suggested Relationship in the Pathogenesis of Diabetic Neuropathy , 1983, Diabetes.

[21]  D. Greene.  Metabolic abnormalities in diabetic peripheral nerve: relation to impaired function. , 1983, Metabolism: clinical and experimental.

[22]  R. Schmidt,et al.  The Effect of Pancreatic Islet Transplantation and Insulin Therapy on Experimental Diabetic Autonomic Neuropathy , 1983, Diabetes.

[23]  A. Sima,et al.  Axonal atrophy in sensory nerves of the diabetic BB‐Wistar rat: A possible early correlate of human diabetic neuropathy , 1983, Annals of neurology.

[24]  D. Felten,et al.  Neuropathic changes associated with insulin treatment of diabetic rats: Electron microscopic and morphometric analysis , 1983, Brain Research Bulletin.

[25]  A. Andersson,et al.  EFFECTS OF PANCREATIC ISLET IMPLANTATION ON THE MORPHOLOGY OF RETINAL CAPILLARIES IN ALLOXAN DIABETIC MICE , 1983, Acta ophthalmologica.

[26]  D. B. Martin,et al.  Has one diabetic complication been explained? , 1983, The New England journal of medicine.

[27]  A. Sima,et al.  Proximal Motor Neuropathy in the BB-Wistar Rat , 1982, Diabetes.

[28]  R. Schmidt,et al.  Axonal Dystrophy in Experimental Diabetic Autonomic Neuropathy , 1982, Diabetes.

[29]  A. Winegrad,et al.  Significance of tissue myo-inositol concentrations in metabolic regulation in nerve. , 1982, Science.

[30]  T. Brismar,et al.  Changes in nodal function in nerve fibres of the spontaneously diabetic BB-Wistar rat: potential clamp analysis. , 1981, Acta physiologica Scandinavica.

[31]  S. Brimijoin,et al.  Retrograde Axonal Transport of Transmitter Enzymes, Fucose-Labeled Protein, and Nerve Growth Factor in Streptozotocin-Diabetic Rats , 1981, Diabetes.

[32]  A. Sima,et al.  FUNCTIONAL ASPECTS AND PATHOGENETIC CONSIDERATIONS OF THE NEUROPATHY IN THE SPONTANEOUSLY DIABETIC BB‐WISTAR RAT , 1981, Neuropathology and applied neurobiology.

[33]  R. Schmidt,et al.  Experimental diabetic autonomic neuropathy. , 1981, The American journal of pathology.

[34]  A. Windebank,et al.  Interstitial Hyperosmolarity May Cause Axis Cylinder Shrinkage in Streptozotocin Diabetic Nerve , 1980, Journal of neuropathology and experimental neurology.

[35]  J. Jakobsen,et al.  Early and preventable changes of peripheral nerve structure and function in insulin-deficient diabetic rats. , 1979, Journal of neurology, neurosurgery, and psychiatry.

[36]  S. Yagihashi,et al.  Peripheral nerve structures of experimental diabetes rats and the effect of insulin treatment. , 1979, The Tohoku journal of experimental medicine.

[37]  P. Thomas,et al.  Peripheral Nerve Fiber Size in Experimental Diabetes , 1977, Diabetes.

[38]  A. Tingle,et al.  The use of hypaque-ficoll in the isolation of pancreatic islets in rats. , 1976, Transplantation.

[39]  D. Worthen,et al.  Effect of whole pancreas transplantation on eye lesions of alloxan diabetes. , 1976, Surgical forum.

[40]  D. A. Godfrey,et al.  Fast and Slow Axoplasmic Flow in Sciatic Nerve of Diabetic Rats , 1975, Diabetes.

[41]  D. Greene,et al.  Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. , 1975, The Journal of clinical investigation.

[42]  P K Thomas,et al.  Peripheral nerve structure and function in experimental diabetes. , 1974, Journal of the neurological sciences.

[43]  M. Ziegler,et al.  Physiological and immunological consequences of transplanting isolated pancreatic islets. , 1973, Surgery.