Low-intensity Pulsed Ultrasound Stimulation of the Intestine Improves Insulin Resistance in Type 2 Diabetes

Ultrasound stimulation of internal organs and peripheral nerves has demonstrated promising potential in regulating blood glucose metabolism. This study aims to assess the effectiveness of low-intensity pulsed ultrasound stimulation (LIPUS) on intestine in improving insulin resistance with type 2 diabetes mellitus (T2DM).

C57BL/6J mice, both normal and T2DM, were randomly divided into three groups: Control, T2D-sham, and T2D-LIPUS. The T2D-LIPUS group received LIPUS stimulation in the intestine. The parameters were as follows: 1 MHz frequency, 1.0 kHz pulse repetition frequency (PRF), 20% duty cycle, 100 mW/cm² intensity spatial average temporal average (I_SATA), for 20 minutes per session, five days per week, over four weeks.

Blood glucose analysis indicated that mice in the T2D-LIPUS group displayed significantly lower area under the curve (AUC) of glucose tolerance tests (GTT) and insulin tolerance tests (ITT) (p < 0.001), HOMA-IR (p < 0.001), and fasting serum insulin levels (p < 0.01) compared to the T2D-sham group. LIPUS treatment effectively lowered serum levels of IL-1β (p < 0.001) and TNF-α (p < 0.01) along with mRNA expression levels of IL-1β (p < 0.01) and IL-18 (p < 0.001) in the intestines of T2DM mice. Additionally, Western blot analysis revealed a reduction in the protein levels of NLRP3, caspase-1, and GSDMD-N in the intestinal tissues of mice treated with LIPUS.

These findings suggest that LIPUS can reduce inflammation and cellular apoptosis, while improving insulin resistance by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway. This research introduces a novel, non-pharmacological approach for managing T2DM.