Department of Biomedical Engineering Posters and Presentations

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells

Poster Number

109

Document Type

Poster

Publication Date

3-2016

Abstract

OBJECTIVE : Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. Thus, new modes of therapy are needed that will directly target the underlying causes of impaired glucose homeostasis. 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 focus on determination of 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 cultured INS-1 beta cells. Effects of ultrasound on cell viability were assessed by trypan blue exclusion method. Planar ultrasound transducers with center frequencies of 400 kHz,600 kHz, 800 kHz and 1 MHz were used to expose cells for a duration of 5 minutes at an intensity of 1 W/cm2. Insulin release and cell viability results were studied as a function of temperature increase and non-thermal activity as measured experimentally and simulated using PZFlex modeling software.

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. However, cell viability was highly reduced (by around 80-90%) when the cells were exposed to ultrasound frequencies of 400 kHz and 600 kHz(p < 0.001). ELISA results showed that significant amounts of insulin were released from beta cells exposed to 400kHz and 600 kHz ultrasound at the cost of cell viability (p < 0.05). Cell exposure to ultrasound at frequency of 800 kHz resulted in approximately 4-fold increase in insulin release (p < 0.005). Cell exposure to ultrasound at frequency of 1MHz also showed increased insulin release (around 50%) though no statistical significance was achieved when compared to sham treatment

CONCLUSIONS: If shown successful our approach may eventually lead to new methods in the treatment of diabetes and other secretory diseases. Our future studies will focus on application of ultrasound to human pancreatic islets to determine whether it would be possible to stimulate beta cells without stimulating other endocrine and exocrine cells of the pancreas.

Creative Commons License

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

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Presented at: GW Research Days 2016

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Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells

OBJECTIVE : Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. Thus, new modes of therapy are needed that will directly target the underlying causes of impaired glucose homeostasis. 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 focus on determination of 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 cultured INS-1 beta cells. Effects of ultrasound on cell viability were assessed by trypan blue exclusion method. Planar ultrasound transducers with center frequencies of 400 kHz,600 kHz, 800 kHz and 1 MHz were used to expose cells for a duration of 5 minutes at an intensity of 1 W/cm2. Insulin release and cell viability results were studied as a function of temperature increase and non-thermal activity as measured experimentally and simulated using PZFlex modeling software.

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. However, cell viability was highly reduced (by around 80-90%) when the cells were exposed to ultrasound frequencies of 400 kHz and 600 kHz(p < 0.001). ELISA results showed that significant amounts of insulin were released from beta cells exposed to 400kHz and 600 kHz ultrasound at the cost of cell viability (p < 0.05). Cell exposure to ultrasound at frequency of 800 kHz resulted in approximately 4-fold increase in insulin release (p < 0.005). Cell exposure to ultrasound at frequency of 1MHz also showed increased insulin release (around 50%) though no statistical significance was achieved when compared to sham treatment

CONCLUSIONS: If shown successful our approach may eventually lead to new methods in the treatment of diabetes and other secretory diseases. Our future studies will focus on application of ultrasound to human pancreatic islets to determine whether it would be possible to stimulate beta cells without stimulating other endocrine and exocrine cells of the pancreas.