Correction of protein kinase C activity and macrophage migration in peripheral nerve by pioglitazone, peroxisome proliferator activated‐γ‐ligand, in insulin‐deficient diabetic rats

Yamagishi, Shin‐Ichiro; Ogasawara, Saori; Mizukami, Hiroki; Yajima, Nobuhisa; Wada, Ryuichi; Sugawara, Akiko; Yagihashi, Soroku

doi:10.1111/j.1471-4159.2007.05050.x

Cited by 79 publications

(76 citation statements)

References 52 publications

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“…PPAR-gamma agonists are similarly protective in models of multiple sclerosis [82], amyotrophic lateral sclerosis [83], Parkinson's disease [84], and Alzheimer's disease [85,86]. Furthermore PPARgamma agonists also protect against diabetic neuropathy [87,88]. It should be noted that since germline PPAR-gamma knockout mice are not viable, it has not been possible to demonstrate genetically that protective effects of PPARgamma agonists are necessarily mediated by PPAR-gamma.…”

Section: Neuroprotective Effects Of Ppargamma Agonistsmentioning

confidence: 99%

Neuroprotection by dietary restriction and the PPAR transcription complex

Mobbs

Moreno

Kim

et al. 2012

Translational Neuroscience

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Although the pathophysiology of neurodegenerative diseases is distinct for each disease, considerable evidence suggests that a single manipulation, dietary restriction, is strikingly protective against a wide range of such diseases. Thus pharmacological mimetics of dietary restrictions could prove widely protective across a range of neurodegenerative diseases. The PPAR transcription complex functions to re-program gene expression in response to nutritional deprivation as well as in response to a wide variety of lipophilic compounds. In mammals there are three PPAR homologs, which dimerize with RXR homologs and recruit coactivators Pgc1-alpha and Creb-binding protein (Cbp). PPARs are currently of clinical interest mainly because PPAR activators are approved for use in humans to reduce lipidemia and to improve glucose control in Type 2 diabetic patients. However, pharmacological enhancement of the activity of the PPAR complex is neuroprotective across a wide variety of models for neuropathological processes, including stroke, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Conversely activity of the PPAR transcriptional complex is reduced in a variety of neuropathological processes. The main mechanisms mediating the neuroprotective effects of the PPAR transcription complex appear to be re-routing metabolism away from glucose metabolism and toward alternative subtrates, and reduction in inflammatory processes. Recent evidence suggests that the PPAR transcriptional complex may also mediate protective effects of dietary restriction on neuropathological processes. Thus this complex represents one of the most promising for the development of pharmacological treatment of neurodegenerative diseases.

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Section: Neuroprotective Effects Of Ppargamma Agonistsmentioning

confidence: 99%

Neuroprotection by dietary restriction and the PPAR transcription complex

Mobbs

Moreno

Kim

et al. 2012

Translational Neuroscience

View full text Add to dashboard Cite

show abstract

“…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%

“…However, it has been shown that hyperglycemia in diabetic patients is the main factor of diabetic neuropathies induces oxidative stress through various cellular pathways such as increasing aldose reductase activity (Srivastava et al, 2005), increasing glycation end-products (Sugimoto et al, 2008) and altering protein kinas C activity (Yamagishi et al, 2008). Additionally, longstanding hyperglycemia induced oxygen free radicals can damage mitochondrial DNA in dorsal root ganglia leading to peripheral nerves dysfunction (Schmeichel et al, 2003;Arora et al, 2008;Sharma et al, 2009).…”

Section: Introductionmentioning

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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“…Hyperglycemia in diabetic patients as the main factor of diabetic neuropathy induces oxidative stress through various cellular pathways such as increasing aldose reductase activity (Srivastava et al, 2005), increasing glycation end-products (Sugimoto et al, 2008) and altering protein kinas C activity (Yamagishi et al, 2008). Longstanding hyperglycemia through producing a large amount of Reactive Oxygen Species (ROS) can damage mitochondrial DNA in dorsal root ganglia leading to peripheral nerves dysfunction (Schmeichel et al, 2003).…”

Section: Introductionmentioning

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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Correction of protein kinase C activity and macrophage migration in peripheral nerve by pioglitazone, peroxisome proliferator activated‐γ‐ligand, in insulin‐deficient diabetic rats

Cited by 79 publications

References 52 publications

Neuroprotection by dietary restriction and the PPAR transcription complex

Neuroprotection by dietary restriction and the PPAR transcription complex

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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