Gut-on-a-chip platform dynamically monitors GLP-1 secretion from primary intestinal tissue, outperforming static methods

Understanding the dynamic secretion of glucagon-like peptide-1 (GLP-1), a key incretin hormone from enteroendocrine L-cells, is crucial for developing therapies for obesity and type 2 diabetes. Current in vitro methods, such as static incubation of immortalized cell lines or primary tissues, lack physiological relevance and cannot capture the dynamic nature of hormone release. This limitation hinders mechanistic studies and the efficient screening of novel GLP-1 secretagogues, creating a significant gap in drug discovery for metabolic disorders.

Researchers developed a gut-on-a-chip (GOC) platform using a polymethyl methacrylate microchip designed to house primary mouse intestinal tissue. The platform supports parallel luminal and serosal perfusion via peristaltic microfluidic pumps, mimicking physiological conditions. They initially characterized regional GLP-1 secretion capacity along the mouse small intestine. In proof-of-concept experiments, physiological GLP-1 secretagogues like taurocholic acid and glucose were delivered to duodenal and colonic tissue surfaces under continuous or intermittent perfusion, comparing the GOC's performance against traditional static incubation methods.

The developed gut-on-a-chip platform demonstrated significant superiority over static incubation for studying GLP-1 secretion in primary intestinal tissue. It successfully captured dynamic serosal concentration changes of GLP-1 over 2 h, a capability lacking in static models. Furthermore, the GOC platform better preserved tissue viability and morphology throughout the experimental period, indicating a more biomimetic environment for sustained tissue function. This enhanced preservation is critical for long-term studies of gut hormone release. The platform's ability to monitor real-time changes under controlled flow conditions provides a more accurate representation of in vivo physiology.

The gut-on-a-chip platform showed superiority over static incubation for studying GLP-1 secretion, capturing dynamic serosal concentration changes over 2 h while better preserving tissue viability and morphology.