Investigating the Impact of Low-Intensity Therapeutic Ultrasound on Hormonal Regulation in the Pancreas
Open Access DepositedAbstract of Dissertation Investigating the Impact of Low-Intensity Therapeutic Ultrasound on Hormonal Regulation in the Pancreas A clinically promising approach gaining momentum involves leveraging the therapeutic potential of low-intensity ultrasound to elicit systemic responses. Previous research conducted in our lab demonstrated the capacity of this modality to stimulate insulin release and induce biologically significant alterations in pancreatic tissue across various models, including primary cell lines and human pancreatic islet cells from donors. These findings have prompted further investigation into the effects of therapeutic ultrasound, both in vitro and in vivo, with a specific focus on hormonal regulation of pancreatic secretagogues, such as insulin and glucagon. One significant application of this approach lies in its potential as a non-invasive therapy for managing type 2 diabetes mellitus, a widespread and complex metabolic disorder. The appeal of therapeutic ultrasound in this context stems from its ability to induce bioeffects while selectively targeting deep tissues, facilitating the modulation of hormone secretion within the pancreas. In this dissertation, we studied the usability of therapeutic ultrasound in combating type 2 diabetes, emphasizing its potential to induce specific biological effects deep within tissues. Using low-intensity ultrasound at a frequency of 800 kHz and an intensity of 0.5 W/cm², we conducted experiments on insulinoma β-cell lines, human pancreatic islet cell models, and excised rat pancreases to assess hormonal regulation at various physiological levels. Initially, we evaluated the influence of ultrasound on gene expression in human pancreatic islets using RT-qPCR analysis, placing emphasis on the regulation of insulin, glucagon, amylin, and binding immunoglobulin protein (BiP). Subsequently, we employed computational modeling and experimental perfusion systems to investigate the effects of ultrasound on insulinoma β-cells, focusing on both thermal and mechanical impacts. Real-time analysis of insulin and amylin secretion was performed using enzyme-linked immunosorbent assays (ELISA) to assess the immediate effects of ultrasound treatment. Further experimentation involved applying low-intensity ultrasound to excised rat pancreases, followed by ELISA analysis of insulin, glucagon, and alpha-amylase secretion. The observed effects warrant continued exploration of therapeutic ultrasound in pancreatic modulation. Future studies should aim to deepen our understanding of the mechanisms underlying ultrasound-mediated effects in the pancreas and their potential clinical implications for diabetes management.
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