The protective effect of metformin on mitochondrial dysfunction and endoplasmic reticulum stress in diabetic mice brain

European Journal of Pharmacology
Taskeen Fathima DocratAnil A Chuturgoon

Abstract

Diabetes is a metabolic disorder associated with mitochondrial (mt) dysfunction and oxidative stress. The molecular mechanisms involved in diabetes-associated neurological complications remain elusive. This study aims to investigate the protective effect of metformin (MF) on regulatory networks and integrated stress responses in brain tissue of Streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were treated with MF (20 mg/kg BW), and whole brain tissue was harvested for further analysis. Protein carbonylation was measured as a marker of neuronal oxidative stress. Protein expression of mt chaperones, maintenance proteins, and regulators of the unfolded protein response (UPR) were measured by Western blot. Transcript levels of antioxidant enzyme GSTA4; mt biogenesis markers, ER stress regulators, and miR-132 and miR-148a were analysed using qPCR. The results showed that MF efficiently reduced protein carbonylation and oxidation. Mt function was improved by MF-treatment through upregulation of chaperone proteins (HSP60, HSP70 and LonP1). MF elicits the UPR to attenuate ER stress through a miR-132 repression mechanism. Additionally, MF was found to elevate deacetylases- Sirt1, Sirt3; and mt biogenesis marker PGC-...Continue Reading

Citations

Sep 12, 2020·International Journal of Molecular Sciences·Konstantin N BelosludtsevMikhail V Dubinin
Oct 6, 2020·Frontiers in Physiology·Ruben Coronel
Nov 5, 2020·Journal of Biochemical and Molecular Toxicology·Forouzan KhodaeiMohsen Rezaei
Sep 27, 2020·Diabetes Care·Lars Vedel KessingThomas Alexander Gerds
Feb 23, 2021·Brain Research Bulletin·Anna ThinnesJochen Klein
Mar 12, 2021·Endocrine Reviews·Amir AjoolabadyJun Ren
Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Nahid AlimoradiReihaneh Fatehi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Diabetes

This feed focuses on the latest research on biomarkers used for monitoring disease progression in diabetes.