Physiological Gut Oxygenation Alters GLP-1 Secretion from the Enteroendocrine Cell Line STC-1

Enteroendocrine cell lines are routinely assayed in simple buffers at ≈20% oxygen to screen foods for bioactives that boost satiety hormone levels. However, in vivo, enteroendocrine cells are exposed to different phases of food digestion and function at low oxygen concentration, ranging from 7.5% in the stomach to 0.5% in the colon-rectal junction.

The objective of this study is to investigate the effect of physiologically relevant O₂ concentrations of the gut on the production and secretion of the satiety hormone, glucagon-like peptide 1 (GLP-1), from the murine enteroendocrine cell line, secretin tumor cell line (STC-1), in response to dairy macronutrients as they transit the gut. GLP-1 exocytosis from STC-1 cells is influenced by both oxygen concentration and by individual macronutrients. At low oxygen, STC-1 cell viability is significantly improved for all macronutrient stimulations and cyclic adenosine monophosphate levels are dampened. GLP-1 secretion from STC-1 cells is influenced by both the phase of yogurt digestion and corresponding O₂ concentration. Atmospheric oxygen at 4.5% combined with upper gastric digesta, which simulates ileum conditions, yields the highest GLP-1 response.

This demonstrates the importance of considering physiological oxygen levels and food digestion along gastrointestinal tract for reliable in vitro analysis of gut hormone secretion.