Non-invasive glycemic control leveraging ultrasound dose window activation of MscL in diabetic mice

Type 2 diabetes is characterized by impaired glucose homeostasis and progressive pancreatic β cell dysfunction, highlighting the need for externally controllable strategies for metabolic regulation. Here, we combined low-intensity pulsed ultrasound (LIPUS) with the mechanosensitive channel MscL-G22S to establish a tunable sonogenetic system for glucose regulation. Graded ultrasound stimulation was evaluated in MscL-G22S-expressing β cells and diabetic db/db mice to define an effective acoustic dose range. Within an intermediate dose window, LIPUS increased intracellular Ca²⁺ levels and glucose-stimulated insulin secretion in vitro and improved glycemic control, insulin sensitivity, islet morphology, and systemic metabolic profiles in vivo. Serum metabolomics further identified metabolic pathway alterations associated with combined LIPUS and MscL-G22S activation. These findings establish a quantitative framework for relating ultrasound dose to sonogenetic metabolic responses and support further investigation of ultrasound-controlled regulation of glucose homeostasis.