Intranasal insulin improves the structure–function of the brain mitochondrial ATP–sensitive Ca2+ activated potassium channel and respiratory chain activities under diabetic conditions
| Autor: | Javad Fahanik-Babaei, Maryam Nazari, Reza Saghiri, Nihad Torabi, Afsaneh Eliassi, Farzad Shayanfar, Elham Noursadeghi, Fariba Khodagholi |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS medicine.diagnostic_test Chemistry Insulin medicine.medical_treatment Respiratory chain Mitochondrion medicine.disease Potassium channel Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Mitochondrial respiratory chain Western blot Diabetes mellitus medicine Molecular Medicine Molecular Biology 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1867:166075 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2021.166075 |
| Popis: | Although it is well established that diabetes impairs mitochondrial respiratory chain activity, little is known of the effects of intranasal insulin (INI) on the mitochondrial respiratory chain and structure-function of mitoBKCa channel in diabetes. We have investigated this mechanism in an STZ-induced early type 2 diabetic model. Single ATP-sensitive mitoBKCa channel activity was considered in diabetic and INI-treated rats using a channel incorporated into the bilayer lipid membrane. Because mitoBKCa channels have been involved in mitochondrial respiratory chain activity, a study was undertaken to investigate whether the NADH, complexes I and IV, mitochondrial ROS production, and ΔΨm are altered in an early diabetic model. In this work, we provide evidence for a significant decrease in channel open probability and conductance in diabetic rats. Evidence has been shown that BKCa channel β2 subunits induce a left shift in the BKCa channel voltage dependent curve in low Ca2+ conditions,; our results indicated a significant decrease in mitoBKCa β2 subunits using Western blot analysis. Importantly, INI treatment improved mitoBKCa channel behaviors and β2 subunits expression up to ~70%. We found that early diabetes decreased activities of complex I and IV and increased NADH, ROS production, and ΔΨm. Surprisingly, INI modified the mitochondrial respiratory chain, ROS production, and ΔΨm up to ~70%. Our results thus demonstrate an INI improvement in respiratory chain activity and ROS production in brain mitochondrial preparations coming from the STZ early diabetic rat model, an effect potentially linked to INI improvement in mitoBKCa channel activity and channel β2 subunit expression. |
| Databáze: | OpenAIRE |
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