Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons
Open accessAbstract
Background: Accumulated evidence suggests that hydrogen peroxide (H 2 O 2) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H 2 O 2 in neuronal insulin receptor activation and the origin of insulin-induced H 2 O 2 in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H 2 O 2 is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H 2 O 2 production, thus playing an integral role in insulin receptor autophosphorylation in neurons. Results: Insulin stimulation elicited rapid insulin receptor autophosphorylation accompanied by an increase in H 2 O 2 release from cultured cerebellar granule neurons (CGN). N-acetylcysteine (NAC), a H 2 O 2 scavenger, inhibited both insulin-stimulated H 2 O 2 release and insulin-stimulated autophosphorylation of insulin receptor. Inhibitors of respiratory chain-mediated H 2 O 2 production, malonate and carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), inhibited both insulin-stimulated H 2 O 2 release from neurons and insulin-stimulated autophosphorylation of insulin receptor. Dicholine salt of succinic acid, a respiratory substrate, significantly enhanced the effect of suboptimal insulin concentration on the insulin receptor autophosphorylation in CGN. Conclusion: Results of the present study suggest that insulin-induced H 2 O 2 is required for the enhancement of insulin receptor autophosphorylation in neurons. The mitochondrial respiratory chain is involved in insulin-stimulated H 2 O 2 production, thus playing an integral role in the insulin receptor autophosphorylation in neurons.
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Mitochondrially produced ROS can activate insulin receptor autophosphorylation after insulin stimulation to promote receptor-mediated actions.
“Furthermore, mitochondrially produced ROS can activate insulin receptor autophosphorylation after insulin stimulation to promote receptor-mediated actions (402).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [402]
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- Authors
- Storozhevykh, T. P., Senilova, Y. E., Persiyantseva, N. A., Pinelis, V. G., & Pomytkin, I. A.
- Affiliations
- Scientific Center of Children's Health (RU)
- ORCID
- Pinelis, Vsevolod G
- Venue
- BMC Neuroscience
- Published
- 2007-10-08
- Volume
- 8
- Issue
- 1
- Pages
- 84-84
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC2089077
- OpenAlex
- W2132357388
- Cited by
- 69
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 9 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 6 · 2013: 4 · 2012: 7
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- insulin receptor autophosphorylation, hydrogen peroxide, mitochondrial respiratory chain, neurons, cerebellar granule cells, insulin signaling, N-acetylcysteine, malonate, FCCP, succinic acid, reactive oxygen species
- MeSH terms
- Animals, Cells, Cultured, Electron Transport, Hydrogen Peroxide, Insulin, Mitochondria, Neurons, Phosphorylation, Receptor, Insulin, Rats, Wistar, Cell Respiration, Rats
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