Department of Biomedical Engineering Posters and Presentations

Title

Ultrasound stimulation of insulin release from pancreatic beta cells as a potential novel treatment for type 2 diabetes

Document Type

Poster

Publication Date

4-2017

Abstract

OBJECTIVE

We are proposing to use therapeutic ultrasound to correct for the inability of the pancreas to secrete insulin in patients with type 2 diabetes (T2D). Controlling T2D is often difficult as pharmacological management routinely requires complex therapy, and loses its effectiveness over time. Thus, there is a growing interest in finding alternative methods for the treatment of this disease. The objective of this study is to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to augment insulin release from pancreatic beta cells.

METHODS
Our experiments focused determining the effectiveness and safety of ultrasound application in stimulation of insulin release from pancreatic beta cells. ELISA insulin release assay was used to determine and quantify the effects of ultrasound on insulin release in INS beta cells. Effects of ultrasound on cell viability were assessed by trypan blue dye exclusion and MTT cytotoxicity assays. Planar ultrasound transducers with center frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz were used to expose cells for different durations at intensities ranging from 0.1 to 1 W/cm2. Carbon fiber amperometry studies were used for studying the temporal dynamics of ultrasound-induced secretory release and coupled with real-time calcium (Ca2+) fluorescence imaging to highlight the role of Ca2+ in this process. Other studies included passive cavitation detection, thermal studies and finite-element modeling of the different experimental setups used in our studies.

RESULTS
Our results indicated that cell viability was not significantly affected during and for up to 30 minutes after treatment when cells were exposed to ultrasound frequencies of 800 kHz and 1 MHz, while keeping their metabolic activity at similar levels compared to the sham group. However, cell viability was highly reduced (by 80-90%) when the cells were exposed to ultrasound frequencies of 400 kHz and 600 kHz (p < 0.001). Cell exposure to ultrasound at frequency of 800 kHz resulted in release of approximately 25 ng/ml/106 cells (p < 0.005) in comparison to no measurable release in cells of the sham group. Amperometry studies suggest that such release is at least partially regulated by Ca2+, an observation supported by increased intracellular Ca2+ during ultrasound exposure as observed with fluorescence imaging.

CONCLUSIONS
If shown successful our approach may lead to new methods in the treatment of diabetes and other secretory diseases. Our future studies will focus on application of optimized ultrasound parameters to more physiologically-relevant models such as human pancreatic islets and animal stud

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

Comments

To be presented at GW Annual Research Days 2017.

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Ultrasound stimulation of insulin release from pancreatic beta cells as a potential novel treatment for type 2 diabetes

OBJECTIVE

We are proposing to use therapeutic ultrasound to correct for the inability of the pancreas to secrete insulin in patients with type 2 diabetes (T2D). Controlling T2D is often difficult as pharmacological management routinely requires complex therapy, and loses its effectiveness over time. Thus, there is a growing interest in finding alternative methods for the treatment of this disease. The objective of this study is to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to augment insulin release from pancreatic beta cells.

METHODS
Our experiments focused determining the effectiveness and safety of ultrasound application in stimulation of insulin release from pancreatic beta cells. ELISA insulin release assay was used to determine and quantify the effects of ultrasound on insulin release in INS beta cells. Effects of ultrasound on cell viability were assessed by trypan blue dye exclusion and MTT cytotoxicity assays. Planar ultrasound transducers with center frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz were used to expose cells for different durations at intensities ranging from 0.1 to 1 W/cm2. Carbon fiber amperometry studies were used for studying the temporal dynamics of ultrasound-induced secretory release and coupled with real-time calcium (Ca2+) fluorescence imaging to highlight the role of Ca2+ in this process. Other studies included passive cavitation detection, thermal studies and finite-element modeling of the different experimental setups used in our studies.

RESULTS
Our results indicated that cell viability was not significantly affected during and for up to 30 minutes after treatment when cells were exposed to ultrasound frequencies of 800 kHz and 1 MHz, while keeping their metabolic activity at similar levels compared to the sham group. However, cell viability was highly reduced (by 80-90%) when the cells were exposed to ultrasound frequencies of 400 kHz and 600 kHz (p < 0.001). Cell exposure to ultrasound at frequency of 800 kHz resulted in release of approximately 25 ng/ml/106 cells (p < 0.005) in comparison to no measurable release in cells of the sham group. Amperometry studies suggest that such release is at least partially regulated by Ca2+, an observation supported by increased intracellular Ca2+ during ultrasound exposure as observed with fluorescence imaging.

CONCLUSIONS
If shown successful our approach may lead to new methods in the treatment of diabetes and other secretory diseases. Our future studies will focus on application of optimized ultrasound parameters to more physiologically-relevant models such as human pancreatic islets and animal stud