Figure 6.

Intestinal epithelial cell RAS and B⁰AT1 govern glucose, sodium, and inflammation. All RAS components are recapitulated locally in the gut (41). Luminal agonist and antagonist bioactive peptides are derived from interactions of gut digestive enzymes intertwined with microbiome metabolism. Oral ARBs and ACE inhibitor drugs impact gut RAS. Gut RAS governs sodium and glucose uptake via NHE3, SGLT1, and GLUT2. The ACE2:B⁰AT1 complex dimer of heterodimers (18) serves the Na⁺-coupled transport of neutral amino acids, including tryptophan. In enteroendocrine L cells, basolateral tryptophan stimulates GLP-1 and GIP secretion. These incretins maintain gut tight junctions, preventing dysbiosis, stimulate pancreatic β-cells, and blunt α-cells, thereby modulating plasma glucose levels. SARS-CoV-2 binding to ACE2 disrupts this homeostasis.