The neuropathies associated with diabetes mellitus

Mulder, Donald W.; Lambert, Edward H.; Bastron, James A.; Sprague, Randall G.

doi:10.1097/00132985-196104000-00001

Cited by 108 publications

(33 citation statements)

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“…Clinical and electrophysiological studies on human diabetic patients have also suggested that diabetic nerves are more susceptible to compression trauma than normal nerves [1,34,35]. Thus, there are several experimental and clinical studies which indicate, in accordance with the present study, that diseased neurones in diabetes mellitus may be more susceptible to compression trauma [9].…”

Section: Discussionsupporting

confidence: 88%

“…Sensory and muscular dysfunction in extremities may, however, also be caused by entrapment of peripheral nerves such as ulnar nerve compression at the elbow and median nerve compression at the wrist, i. e. the carpal tunnel syndrome. A high frequency of such mononeuropathies has been reported among diabetic patients, which suggests enhanced vulnerability of peripheral nerves to trauma [1]. It has also been suggested that peripheral nerves in experimental diabetes have a greater susceptibility to injury [2][3][4].…”

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confidence: 99%

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Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus

McLean

et al. 1986

Diabetologia

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Summary. The hypothesis that nerves in diabetes mellitus exhibit an increased susceptibility to compression was experimentally tested. Inhibition of fast axonal transport was induced by local compression in sciatic nerves of rats with streptozotocin-induced diabetes mellitus. Fast anterograde axonal transport was measured after application of 3H-leucine to the motor neurone cell bodies in the spinal cord. The sciatic nerve was subjected to local, graded compression in vivo by a small compression chamber. The amount of accumulation of proteins was quantified by calculation of a transport block ratio. Compression at 30 mm Hg for 3 h induced a significantly greater (p<0.05) accumulation of axonally transported proteins at the site of compression in nerves of diabetic animals (transport block ratio: 1.01_+0.35; n=7) than in nerves of controls (0.67 + 0.16; n = 7). Accumulation was significantly higher in ligature experiments of both control (1.34_+ 0.44; n = 8; p < 0.01) and diabetic animals (1.45 _+ 0.30; n = 8; p < 0.05), indicating that the block of transport in compressed nerves was incomplete. Neither sham compressed diabetic (0.50+0.09; n=6) nor control (0.49_+0.11; n=6) nerves showed any block of axonal transport. The possible causes of the increased inhibition of fast axonal transport in diabetic rats are discussed. The results indicate that diabetes may lead to an increased susceptibility of peripheral nerves to compression.Key words: Compression, diabetes mellitus, streptozotocin, axonal transport, compression syndromes, mononeuropathy, neuropathy.The clinical symptoms of neuropathy in diabetes mellitus are well known, and include primarily sensory complaints, occasionally accompanied by muscular weakness and autonomic symptoms. Sensory and muscular dysfunction in extremities may, however, also be caused by entrapment of peripheral nerves such as ulnar nerve compression at the elbow and median nerve compression at the wrist, i. e. the carpal tunnel syndrome. A high frequency of such mononeuropathies has been reported among diabetic patients, which suggests enhanced vulnerability of peripheral nerves to trauma [1]. It has also been suggested that peripheral nerves in experimental diabetes have a greater susceptibility to injury [2][3][4].Axonopathy, which can be characterised by abnormalities in axonal transport, may be an important factor in the neuropathies which accompany diabetes [5][6][7]. Based upon previous experience on the effects of peripheral nerve compression [for review see 8] and the hypothesis that diseased neurones, such as those in diabetes mellitus, are more susceptible to compression * Present address: Department of Anatomy and Neurobiology, Washington University, School of Medicine, St. Louis, Missouri, USA trauma than are healthy neurones [9], we decided to investigate the effects of experimental nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus Materials and methods Animals and induction of diabetesRandom-bred and weight-matched female Sprague-Dawle...

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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus

McLean

et al. 1986

Diabetologia

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“…A number of reports (21-.24) suggest that the neuropathy ofdiabetes mellitus may involve altered tubulin-microtubule function (25). Axonal shortening (26), decreased axonal flow (27), increased latency (28), and reduced conduction velocities (29) Tables 1 and 2 (in particular those for incubation with glucose 6-phosphate at 10 mg/ml) leads to the suggestion that colchicine may partially inhibit the formation of tubulin aggregates after glycosylation.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.

Williams¹,

Howarth²,

Devenny³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

110

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The extent ofin vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTPdependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.Diabetes mellitus is often accompanied by the gradual development of diverse and multifocal pathology (1). Insulin and antibiotics have contributed substantially to the management of carbohydrate abnormalities and infection (2). However, deterioration in the microcirculation of retina and kidney and diabetic neuropathy continue to present serious clinical problems (3). It is still unclear whether these complications are uniquely the result of carbohydrate disturbances due to intermittent insulin deficiency or also reflect more subtle genetic or metabolic factors that are, at best, indirectly related to insulin levels (4).Recent data have supported the hypothesis that increased nonenzymatic as well as enzymatic glycosylation ofcellular components, as a result of the elevated glucose concentrations of diabetes, may play a contributory role in diabetic microangiopathy (5), and diabetic cataractogenesis (6). Modification, by the nonenzymatic addition of glucose, has now been reported for a variety of serum, cellular, and interstitial proteins and phospholipids (7-10), suggesting the possibility that unanticipated additional functional changes may yet be observed to result from nonenzymatic (or enzymatic) glycosylation.We present here evidence for in vitro and in vivo glycosylation of brain tubulin as a consequence of exposure to elevated glucose concentrations. The in vitro nonenzymatic glycosylation oftubulin results in the formation ofamorphous aggregates oftubulin and tubulin-associated proteins that remain insoluble in 8 M urea or NaDodSO4. The in vivo formation of glycosylation-induced tubulin aggregates was found to compete with ordered tubulin polymerization in diabetic rats. METHODS AND MATERIALSTubulin Isolation and Measurement. Tubulin was purified from male weanling Sprague-Dawley rat brain according to the procedure of Berkowitz et al. (11). Rats were sacrificed by occipital trauma and cervical dislocation. Brains were removed and weighed and 0.75 ml of purification buffer (11) [50 mM 4-morpholineethanesulfonic acid (Sigma)/2 mM EGTA/1 mM MgSO4/4.0 M glycerol, pH 6.9] was added per gram of brain.Brains were homogenized in a loose-fitting motor-driven Teflon/glass homogeniz...

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“…Lateral femoral cutaneous neuropathy. Compression of the lateral femoral cutaneous nerve (meralgia paraesthetica) is uncommon and results in pain, paresthesiae, and sensory loss in the lateral aspect of the thigh (104). Obesity is the most common cause, followed by trauma due to external injury of the nerve, as it runs down the lateral aspect of the thigh.…”

Section: A Mononeuropathiesmentioning

confidence: 99%