Insulin injections inhibits PTZ-induced mitochondrial dysfunction, oxidative stress and neurological deficits via the SIRT1/PGC-1α/SIRT3 pathway

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2021-06, Vol.1867 (6), p.166124-166124, Article 166124
• Main Authors: Cheng, Yahong, Zeng, Xin, Mai, Qianting, Bai, Xinying, Jiang, Yuan, Li, Jinjin, Fan, Shiqi, Ding, Hong
• Format: Article
• Language: English
• Subjects: Epilepsy seizures (SE); Insulin injections; Mitochondrial function; Oxidative stress; SIRT1/ PGC-1α/SIRT3 pathway
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2021.166124

With an associated 20% death risk, epilepsy mainly involves seizures of an unpredictable and recurrent nature. This study was designed to evaluate the neuroprotective effects and underlying mechanisms of insulin on mitochondrial disruption, oxidative stress, cell apoptosis and neurological deficits after epilepsy seizures. Mice were exposed to repetitive injections of pentylenetetrazol at a dose of 37 mg per kg. The influence of insulin was assessed by many biochemical assays, histopathological studies and neurobehavioral experiments. The administration of insulin was proven to increase the latency of seizures while also decreasing their intensity. It also caused a reversal of mitochondrial dysfunction and ameliorated oxidative stress. Additionally, insulin pretreatment upregulated Bcl-2, downregulated Bax, and then played a neuroprotective role against hippocampal neuron apoptosis. Furthermore, when insulin was administered, SIRT1/PGC-1α/SIRT3 signals were activated, possibly due to the fact that insulin's neuroprotective and anti-mitochondrial damage characteristics added to its observed antiepileptic functions. Finally, insulin treatment is thus extremely valuable for effecting improvements in neurological functions, as has been estimated in a series of functional tests. In conclude, the results of this study consequently demonstrate insulin to have significant potential for future application in epilepsy management. [Display omitted] •Insulin injections declined seizure intensity.•Insulin played a neuroprotective role against hippocampal neuron apoptosis.•Neuroprotection of insulin against mitochondrial damage on animals is related to SIRT1/PGC-1α/SIRT3 signaling pathway.