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 Ca 2+ 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.