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Therapeutic Ultrasound-Induced Insulin Release Open Access

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Type 2 diabetes mellitus (T2DM) is a complex and chronic metabolic disease that results from the interplay of systemic insulin resistance of peripheral tissues and insufficient compensatory insulin secretion from pancreatic beta cells (American Diabetes Association, 2010; Kahn, 2001). The objective of this thesis was to investigate the safety and efficacy of low-frequency, low-intensity therapeutic ultrasound-induced insulin release as a non-pharmacological approach for modulating endogenous insulin concentrations in the early stages of T2DM. We utilized a preclinical in vivo murine model and multi-physics computational modeling of the human abdomen to assess the safety, feasibility, and efficacy of the proposed therapy. We observed an increase of 0.30 ± 0.32 ng/mL (mean ± std) in blood insulin concentration in vivo immediately after a five-minute sonication compared to a decrease of 0.37 ± 0.27 ng/mL in sham treated animals in terminal studies (n < 6, p < 0.005). There was no difference observed in the change in glucose or glucagon concentrations between the groups. Comparisons of H&E-stained; terminal and survival pancreatic tissue showed no visible differences or evidence of damage. Computational modeling studies showed that continuous sonication at 1 MHz through a fluid-filled stomach results in a maximum pressure of 181 kPa and maximum temperature of 39.7ºC. This study is the first step is assessing the translational potential of low-frequency, low-intensity therapeutic ultrasound as a potential treatment for the early stages of T2DM as we have demonstrated that it is feasible to safely and effectively modulate insulin release noninvasively.

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