New insights into the metabolic and molecular basis for diabetic neuropathy

Sima, Anders A. F.

doi:10.1007/s00018-003-3084-x

Cited by 150 publications

(161 citation statements)

References 259 publications

(233 reference statements)

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“…Clinically, painful diabetic neuropathy occurs in patients with pre-diabetes (8,9) and early in the course of diabetic neuropathy in type 2 patients (42,43). This has been linked to deficits in neurotrophic factors such as NGF and impaired insulin action with impacts on neuroeffector peptides like substance P and CGRP (36,38,44). These clinical conditions have been explored experimentally in the glucose-intolerant Stockholm-bred GK rat and in the type 2 diabetic BBZDR/Wor rat (10,12).…”

Section: Discussionmentioning

confidence: 99%

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

et al. 2006

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We examined the therapeutic effects of C-peptide on established nociceptive neuropathy in type 1 diabetic BB/Wor rats. Nociceptive nerve function, unmyelinated sural nerve fiber and dorsal root ganglion (DRG) cell morphometry, nociceptive peptide content, and the expression of neurotrophic factors and their receptors were investigated. C-peptide was administered either as a continuous subcutaneous replacement dose via osmopumps or a replacement dose given once daily by subcutaneous injection. Diabetic rats were treated from 4 to 7 months of diabetes and were compared with control and untreated diabetic rats of 4-and 7-month duration. Osmopump delivery but not subcutaneous injection improved hyperalgesia and restored the diabetes-induced reduction of unmyelinated fiber number (P < 0.01) and mean axonal size (P < 0.05) in the sural nerve. High-affinity nerve growth factor (NGF) receptor (NGFR-TrkA) expression in DRGs was significantly reduced at 4 months (P < 0.01). Insulin receptor and IGF-I receptor (IGF-IR) expressions in DRGs and NGF content in sciatic nerve were significantly decreased in 7-month diabetic rats (P < 0.01, 0.05, and 0.005, respectively). Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve. However, subcutaneous injection had only marginal effects on morphometric and molecular changes in diabetic rats. We conclude that C-peptide exerts beneficial therapeutic effects on diabetic nociceptive neuropathy and that optimal effects require maintenance of physiological C-peptide concentrations for a major proportion of the day. Diabetes 55: [3581][3582][3583][3584][3585][3586][3587] 2006

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Section: Discussionmentioning

confidence: 99%

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

et al. 2006

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“…These results are in accordance to Pascoe et al (1997) who demonstrated that diabetes is invariably accompanied by concomitant axonal degeneration that resulted in proximal muscle weakness. Also, in the same line, Sima (2003) suggested that diabetic neuropathy was associated with axonal atrophy.…”

Section: Ajptmentioning

confidence: 87%

“…Peripheral neuropathy is one of the major complains in both types I and II diabetic patients and it is associated with several problems such as cardiovascular defects, retinopathy and muscular pain or weakness (Yamagishi et al, 2008;Sima, 2003;Rajbhandari and Piya, 2005). Since these defects affect the quality and quantity of life, treatment of diabetic neuropathy or prevention of its accompanying symptoms has been considered as a major goal in the recent decades.…”

Section: Discussionmentioning

confidence: 99%

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Bin-Jaliah¹

2014

American Journal of Pharmacology and Toxicology

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It was shown that hyperglycemia in diabetic patients is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the development of diabetic peripheral neuropathy. A substantial number of studies have shown that antioxidant treatment are promising therapeutics that can prevent or correct reduced motor nerve conduction in diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and streptozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum glucose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction studies of the sciatic nerves of these rats showed decrease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin-E or L-arginine) corrected serum glucose to control values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg −1 and 600 mg kg −1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg −1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion that diabetic peripheral neuropathy is a multifactorial complication, caused by hyperglycemia, oxidative stress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in higher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.

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“…Peripheral neuropathy is one of the major complains in both types I and II diabetic patients and it is associated with several problems such as cardiovascular defects, retinopathy and muscular pain or weakness (Yagihashi et al, 2007;Sima, 2003;Rajbhandari and Piya, 2005). Since these defects affect the quality and quantity of life, treatment of diabetic neuropathy or prevention of its accompanying symptoms has been considered as a major goal.…”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Zangiabadi¹,

Sheibani²,

Asadi-Shekaari³

et al. 2011

American Journal of Pharmacology and Toxicology

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Problem statement: Diabetes mellitus occurs mainly with chronic polyneuropathy, and oxidative stress plays an important role in emergence of most neurologic and behavioral changes in diabetic patients. Many studies have focused on the beneficial effects of various antioxidants such as melatonin on diabetic neuropathy. The aim of this study is to evaluate the effect of melatonin in prevention of neuropathy in Streptozotocin-induced diabetic rats. After prescribing Streptozotocin (STZ), treatment rats received melatonin (10 mg kg day −1 ) or DMSO for a period of 6 weeks. Approach: At the end of the sixth week, non diabetic control group, diabetic control group (sham) and treated rats were examined by thermal pain response tests (hot plate and tail flick). The horizontal and vertical activities of rats were measured in an open field test. After that, Motor Nerve Conduction Velocity (MNCV) of sciatic-tibial nerve recorded. Also, to study morphological alterations resulting from diabetic neuropathy of sciatic nerve, Myelinated Fiber Diameter (MFD), Axon Diameter (AD) and Myelin Sheath Diameter (MSD) were evaluated by light microscope. Results: According to hot plate results, response time to thermal pain at the end of sixth week in sham group showed a significant decrease in comparison with the control group (p<0.01). In hot plate test, although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the open field test, Total Distance Moved (TDM) and mobility duration showed significant decrease in sham and DMSO groups in comparison to the control and melatonin groups. Diabetic rats treated with melatonin showed significant increase in MNCV compared to sham and DMSO groups (p<0.05). In morphological study, pretreatment with Melatonin significantly reversed sciatic nerve diameters (MFD, AD, and MSD) reduction in diabetic rats. Electron microscopy showed myelin splitting and myelin sheath infolding in diabetic control group compare to non diabetic group. Conclusion: This study showed that melatonin can decrease the destructive progress of diabetes and causes neuroprotection against damages resulting from STZinduced hyperglycemia.

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New insights into the metabolic and molecular basis for diabetic neuropathy

Cited by 150 publications

References 259 publications

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

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