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Intranasal insulin improves the structure-function of the brain's mitochondrial ATP–sensitive Ca2+ activated potassium channel and respiratory chain activities under diabetic conditions
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Nihad Torabi   , Maryam Nazari , Afsaneh Eliassi |
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Abstract: (242 Views) |
Introduction: Although it is well established that diabetes impairs mitochondrial respiratory chain activity, little is known about the effects of intranasal insulin (INI) on the mitochondrial respiratory chain and the structure of the mitoBKCa channel in diabetes. We have investigated this mechanism in an STZ-induced early type 2 diabetic model.
Methods and Materials: 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.
Results: 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 subunit expression by 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%.
Conclusion: 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.
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| Keywords: Diabetes, Intranasal insulin, Mitochondria, Mitochondrial BKCa channel, Respiratory chain activity |
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Full-Text [PDF 418 kb]
(31 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/31 | Accepted: 2023/08/23 | Published: 2023/08/23
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