Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy.
| Title: | Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy. |
|---|---|
| Authors: | Honma, Hiroyuki1, Podratz, Jewel L.1, Windebank, and Anthony J. |
| Source: | Journal of the Peripheral Nervous System. Jun2003, Vol. 8 Issue 2, p65-74. 10p. |
| Subject Terms: | *GLUCOSE, *DIABETES, *APOPTOSIS, *NEUROPATHY, *IMMUNOCYTOCHEMISTRY |
| Abstract: | Abstract Objective: Our aims were to better understand the mechanisms underlying peripheral neuropathy with diabetes mellitus and to test the hypothesis that acute lowering of glucose levels induces apoptosis in hypoxic neurons. Methods: We used rat dissociated dorsal root ganglion (DRG) neurons incubated in a medium high in glucose concentration (700 mg%) and room air (PO2 150 torr). After 5 days, DRG neurons were placed in hypoxic conditions (PO2 7.6 torr) with a normal-glucose (100 mg%) or high-glucose (700 mg%) medium containing 3 or 100 ng/mL of nerve growth factor. Acute lowering of glucose levels under hypoxic conditions led to apoptosis of DRG neurons. Apoptosis was demonstrated by bis-benzimide staining for nuclear fragmentation, electron microscopy, DNA laddering, and TUNEL staining. Caspase 3 immunocytochemistry and inhibition of neuronal death by the caspase inhibitor z-VAD-fmk (100 μM) confirmed that death was apoptotic. Results: Hypoxia-induced death was decreased when DRG neurons were maintained in high-glucose medium, suggesting that high levels of substrate protected against hypoxia. Apoptosis was completely prevented by increasing the concentration of nerve growth factor from 3 to 100 ng/mL and was partially prevented by the addition of the antioxidant α-lipoic acid (500 μM). Conclusions: This model provides a novel means for studying the pathogenesis and treatment of early stages of diabetic neuropathy. [ABSTRACT FROM AUTHOR] |
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| Database: | Academic Search Complete |
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| Items | – Name: Title Label: Title Group: Ti Data: Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Honma%2C+Hiroyuki%22">Honma, Hiroyuki</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Podratz%2C+Jewel+L%2E%22">Podratz, Jewel L.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Windebank%2C+and+Anthony+J%2E%22">Windebank, and Anthony J.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+the+Peripheral+Nervous+System%22">Journal of the Peripheral Nervous System</searchLink>. Jun2003, Vol. 8 Issue 2, p65-74. 10p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22GLUCOSE%22">GLUCOSE</searchLink><br />*<searchLink fieldCode="DE" term="%22DIABETES%22">DIABETES</searchLink><br />*<searchLink fieldCode="DE" term="%22APOPTOSIS%22">APOPTOSIS</searchLink><br />*<searchLink fieldCode="DE" term="%22NEUROPATHY%22">NEUROPATHY</searchLink><br />*<searchLink fieldCode="DE" term="%22IMMUNOCYTOCHEMISTRY%22">IMMUNOCYTOCHEMISTRY</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract Objective: Our aims were to better understand the mechanisms underlying peripheral neuropathy with diabetes mellitus and to test the hypothesis that acute lowering of glucose levels induces apoptosis in hypoxic neurons. Methods: We used rat dissociated dorsal root ganglion (DRG) neurons incubated in a medium high in glucose concentration (700 mg%) and room air (PO2 150 torr). After 5 days, DRG neurons were placed in hypoxic conditions (PO2 7.6 torr) with a normal-glucose (100 mg%) or high-glucose (700 mg%) medium containing 3 or 100 ng/mL of nerve growth factor. Acute lowering of glucose levels under hypoxic conditions led to apoptosis of DRG neurons. Apoptosis was demonstrated by bis-benzimide staining for nuclear fragmentation, electron microscopy, DNA laddering, and TUNEL staining. Caspase 3 immunocytochemistry and inhibition of neuronal death by the caspase inhibitor z-VAD-fmk (100 μM) confirmed that death was apoptotic. Results: Hypoxia-induced death was decreased when DRG neurons were maintained in high-glucose medium, suggesting that high levels of substrate protected against hypoxia. Apoptosis was completely prevented by increasing the concentration of nerve growth factor from 3 to 100 ng/mL and was partially prevented by the addition of the antioxidant α-lipoic acid (500 μM). Conclusions: This model provides a novel means for studying the pathogenesis and treatment of early stages of diabetic neuropathy. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of the Peripheral Nervous System is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1046/j.1529-8027.2003.03009.x Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 65 Subjects: – SubjectFull: GLUCOSE Type: general – SubjectFull: DIABETES Type: general – SubjectFull: APOPTOSIS Type: general – SubjectFull: NEUROPATHY Type: general – SubjectFull: IMMUNOCYTOCHEMISTRY Type: general Titles: – TitleFull: Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Honma, Hiroyuki – PersonEntity: Name: NameFull: Podratz, Jewel L. – PersonEntity: Name: NameFull: Windebank, and Anthony J. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2003 Type: published Y: 2003 Identifiers: – Type: issn-print Value: 10859489 Numbering: – Type: volume Value: 8 – Type: issue Value: 2 Titles: – TitleFull: Journal of the Peripheral Nervous System Type: main |
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