Insulin-like Growth Factor I Reverses Experimental Diabetic Autonomic Neuropathy

Schmidt, Robert E.; Dorsey, Denise A.; Beaudet, Lucie N.; Plurad, Santiago B.; Parvin, Curtis A.; Miller, Matthew S.

doi:10.1016/s0002-9440(10)65480-6

Cited by 85 publications

(50 citation statements)

References 70 publications

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“…As discussed above, hyperglycemiainduced decreases in neurotrophic factors are well documented, with neurotrophic replacement frequently restoring one or more impaired nerve parameters to normal. Administration of NGF restores neuropeptide levels and sensory amplitudes in experimental diabetes (17,21); in parallel, NT-3 normalizes nerve conduction slowing (22,23) and IGF-I administration blocks the development of neuropathy and reverses impaired nerve regeneration (24,25). When oxidative stress is induced in nerves of nondiabetic animals by administering pro-oxidants, decreases in NGF and NT-3 are observed similar to those reported in animals with experimental diabetes (26).…”

Section: Combination Therapy For the Treatment Of Diabetic Neuropathymentioning

confidence: 69%

Oxidative stress and diabetic neuropathy: a new understanding of an old problem

Feldman¹

2003

J. Clin. Invest.

151

117

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Section: Combination Therapy For the Treatment Of Diabetic Neuropathymentioning

confidence: 69%

Oxidative stress and diabetic neuropathy: a new understanding of an old problem

Feldman¹

2003

J. Clin. Invest.

151

117

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“…A common pathological feature of both human diabetic autonomic neuropathy and experimental diabetic autonomic neuropathy is the presence of neuroaxonal dystrophy in the autonomic ganglia [72,73]. With experimental therapeutics, development of these neuroaxonal pathologies can be prevented or reversed [74,75], but it remains to be seen whether these successes in experimental models of diabetic autonomic neuropathy correspond to clinical successes.…”

Section: Diabetic Neuropathymentioning

confidence: 99%

Animal Models of Peripheral Neuropathies

Höke

2012

Neurotherapeutics

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Peripheral neuropathies are common neurological diseases, and various animal models have been developed to study disease pathogenesis and test potential therapeutic drugs. Three commonly studied disease models with huge public health impact are diabetic peripheral neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus-associated sensory neuropathies. A common theme in these animal models is the comprehensive use of pathological, electrophysiological, and behavioral outcome measures that mimic the human disease.

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“…It has also been reported that up to 90% of patients have subclinical levels of neuropathy. 2 Although several factors have been reported to contribute to diabetic polyneuropathy, [3][4][5][6][7][8][9] the pathogenic basis has remained uncertain. 10 An association between changes in the vasa nervorum and DN has been noted in multiple previous reports; [11][12][13][14][15][16][17] however, the pathophysiologic importance of these observations remains uncertain.…”

mentioning

confidence: 99%

Sonic Hedgehog Induces Arteriogenesis in Diabetic Vasa Nervorum and Restores Function in Diabetic Neuropathy

Kusano

Allendoerfer

Munger

et al. 2004

ATVB

101

109

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Objective-The embryonic morphogen sonic hedgehog (SHh) has been shown to induce neovascularization of ischemic tissue but has not been shown to play a role in regulating vascular nerve supply. Accordingly, we investigated the hypothesis that systemic injection of SHh protein could improve nerve blood flow and function in diabetic neuropathy (DN). Methods and Results-Twelve weeks after induction of diabetes with streptozotocin, motor and sensory nerve conduction velocities (MCV and SCV) of the sciatic nerves were significantly reduced in diabetic rats. SHh-treated diabetic rats demonstrated marked improvement of both MCV and SCV (PϽ0.05). Laser Doppler perfusion imaging showed that nerve blood flow was significantly reduced in the diabetic rats but was restored in SHh-treated diabetic rats (PϽ0.05 versus diabetic saline-treated rats) to levels similar to those achieved with vascular endothelial growth factor-2 (VEGF-2) gene therapy. In vivo perfusion of Bandeuraea simplicifolia (BS)-1 lectin showed marked reduction in the vasa nervora in diabetic sciatic nerves but restoration of nerve vasculature to nondiabetic levels in the SHh-treated and plasmid DNA encoding human VEGF-2 (phVEGF-2)-treated diabetic nerves. Interestingly, the SHh-induced vasculature was characterized by larger diameter and more smooth muscle cell-containing vessels, compared with VEGF-2 gene-treated diabetic rats. Conclusions-These data indicate that Shh induces arteriogenesis and restores nerve function in DN. (Arterioscler ThrombVasc Biol. 2004;24:2102-2107.)Key Words: angiogenesis Ⅲ diabetes mellitus Ⅲ cytokine Ⅲ microcirculation Ⅲ peripheral vasculature I n the United States alone, Ͼ18 million people have diabetes. 1 Diabetic neuropathy (DN) is a frequent complication of diabetes, affecting 1 to 7 million people, including 7% within 1 year of diagnosis and 50% of patients after 25 years. It has also been reported that up to 90% of patients have subclinical levels of neuropathy. 2 Although several factors have been reported to contribute to diabetic polyneuropathy, 3-9 the pathogenic basis has remained uncertain. 10 An association between changes in the vasa nervorum and DN has been noted in multiple previous reports; [11][12][13][14][15][16][17] however, the pathophysiologic importance of these observations remains uncertain. The possibility that attenuation of the vasa nervorum might be a major factor in the development of DN is suggested by several recent studies. Impaired ischemiainduced angiogenesis was noted in animal models of diabetes, 18 and more recently we have reported that both ischemic 19 and DN 20 are associated with attenuation of the vasa nervorum and that local delivery of naked DNA encoding for vascular endothelial growth factor (VEGF-1 and VEGF-2) restores the vascular supply and has a favorable effect on the nerve conduction velocities. These observations, documenting the loss of vasa nervorum in diabetic animals, and restoration of neural vascularity by VEGF, associated with a return of nerve function, suggested that t...

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Insulin-like Growth Factor I Reverses Experimental Diabetic Autonomic Neuropathy

Cited by 85 publications

References 70 publications

Oxidative stress and diabetic neuropathy: a new understanding of an old problem

Oxidative stress and diabetic neuropathy: a new understanding of an old problem

Animal Models of Peripheral Neuropathies

Sonic Hedgehog Induces Arteriogenesis in Diabetic Vasa Nervorum and Restores Function in Diabetic Neuropathy

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