Imaging mechanisms of therapeutic ultrasound in human islets

We have previously shown that therapeutic ultrasound (TUS) has a wide range of effects on rat pancreas cells. We aim to explore additional possible mechanisms of TUS on the pancreas in a more physiologically relevant human islet model with the goal of potential therapies for type-2 diabetes. Fluorescence microscopy was performed on live human islets with dyes that can label for intracellular calcium, sodium, and reactive oxygen species (ROS). During microscopy, TUS was applied at 800 kHz at 0.5 W/cm2 with a pulse repetition frequency of 0.166 Hz and a 16.6% duty cycle. The amount of insulin released from human islets as a result of TUS application was quantified with an enzyme-linked immunoassay (ELISA). Thus far, we have noticed a trend of increased intracellular sodium and ROS generation due to TUS application; however, the percent increase in ROS appears to be less than for intracellular sodium. Our initial ELISA results show that TUS does appear to increase insulin release from human islets (0.55 ± 0.90 μU/ml min) when compared to control (−0.14 ± 0.19 μU/ml min), however, not as much as with the high glucose application at 20 mM (2.47 ± 3.54 μU/ml min). Ongoing studies aim to better characterize TUS effects.