Intranasal insulin improves the structure-function of the brain mitochondrial ATP-sensitive Ca activated potassium channel and respiratory chain activities under diabetic conditions.

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 mitoBK channel in diabetes. We have investigated this mechanism in an STZ-induced early type 2 diabetic model. Single ATP-sensitive mitoBK channel activity was considered in diabetic and INI-treated rats using a channel incorporated into the bilayer lipid membrane. Because mitoBK 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 ΔΨ 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 BK channel β2 subunits induce a left shift in the BK channel voltage dependent curve in low Ca conditions,; our results indicated a significant decrease in mitoBK β2 subunits using Western blot analysis. Importantly, INI treatment improved mitoBK 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 ΔΨ. Surprisingly, INI modified the mitochondrial respiratory chain, ROS production, and ΔΨ 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 mitoBK channel activity and channel β2 subunit expression.