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NF, consisting of heavy, medium, and light subunits, form the major structural lattice of axon. The function of the neurofilaments (NF) is not clear, but abnormal phosphorylation of these proteins is associated with neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson disease, Alzheimer disease, and diabetes (58,59). In diabetes, stress-activated protein kinases are thought to be involved in their aberrant phosphorylation (60,61). Further, abnormal NF accumulation was found in the proximal axon segments of diabetic dorsal root ganglia sensory neurons in human (62), whereas loss of NF in distal nerve terminals of sensory neurons was observed in long-term diabetic rats (63). Impairment in the transport of NF proteins was suspected (64). However, it is not clear whether these changes are the cause or consequences of diabetic lesion.

A line of TG mice that express a fusion protein, where the carboxyl terminus of heavy NF was replaced by P-galactosidase, was found to be completely devoid of peripheral axonal NF, as the fusion protein causes aggregates of NF to precipitate in the perikarya (65). Interestingly, there was no obvious abnormality in the NF-deficient mice except that the caliber of their axons was smaller. In the tibial nerve of these mice the number of fibers and fiber density were higher than that of the WT mice, whereas the axon diameter and axon area were smaller (66). Under normal condition there was no obvious degeneration of their neurons, but the NCV was slower and the amplitude of the nerve action potential was dramatically lower than that of the WT mice, presumably because of the smaller caliber axons. The reduction in SNCV was much more pronounced than the reduction in MNCV. These mice were of Swiss genetic background. When induced to become diabetic, the WT mice exhibited no significant reduction in MNCV and SNCV in their sciatic nerve. The diabetic NF-deficient mice on the other hand, showed significant slowing of MNCV and SNCV. The reduction of the NCV was attenuated by the administration of insulin. Although there was no significant change in the structure of the tibial and sural nerves in the diabetic WT mice, diabetes caused significant decreases in the number of fibers, fiber density, fiber size, axon diameter, and axon area in the tibial nerve of the NF-deficient mice. Similar structural changes were also observed in their sural nerve, except that there was no significant change in the fiber number.

The fact that the NF-deficient mice were more susceptible to diabetes-induced lesions indicates that NF has protective effect on diabetic neuropathy. However, it is not clear whether this finding is relevant to the pathogenesis of the disease in WT animals where slowing of NCV is associated with aberrant phosphorylation of NF rather than the lack of it (60). The decrease in NCV is one of the earliest sign of hyperglycemia-induced lesion, whereas loss of NF occurs only after prolonged hyperglycemia (63). It is possible that loss of NF is the consequence of neuropathy rather than a contributing factor of the disease. The significant NCV slowing and structural abnormalities in the peripheral nerve of the NF-deficient mice before induction of diabetes make interpretation of the results difficult. At this point, it is not clear how the aberrant phosphoryla-tion of NF might contribute to the pathogenesis of diabetic neuropathy.

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Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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