인천대학교 인디고클랫폼 인천대학교 기술지원허브

Obesity-associated diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2DM), are on the rise. Studying the underlying metabolic pathways in these diseases is essential for drug development, requiring advanced in vitro models of the liver-pancreas axis. Existing models support glucose control studies but fail to replicate an in vivo-like liver-pancreas axis due to slow metabolite transport and subpar organ function in mixed media cultures. To overcome these limitations, we developed a multi-organoid device that supports convective transport between separated organoids. This device improves metabolite transport compared to a passive diffusion-based system and enhances organoid function. To recapitulate MASLD, we treated liver organoids with palmitate which triggered representative lipotoxicity, lipid accumulation, and increased secretion of signaling molecule Fetuin A (FetA). Then, our device successfully recapitulated MASLD-triggered T2DM, characterized by FetA-mediated β-cell apoptosis within pancreatic organoids, reduced pancreatic glucose sensitivity, glucose intolerance, and hyperinsulinemia. Furthermore, the well-known T2DM drug metformin demonstrated comparable effects within the device, highlighting its potential utility in drug screening. Overall, this device successfully replicates key MASLD-T2DM interactions, providing a promising tool for studying metabolic diseases and developing treatments.