Fig. 1

Cr/CK shuttle and the intestinal mucosal barrier. Cr is derived from dietary sources in the gastrointestinal tract, or by de novo synthesis synthesis primarily in the liver. The Na⁺ and Cl⁻-dependent creatine transporter (CrT) is expressed in the apical membrane of intestinal epithelial cells, facilitating Cr uptake from the gut lumen. Although intestinal Cr absorption in humans has not been well characterized, potential routes for Cr absorption into systemic circulation include paracellular movement by solvent drag transport, or via basolateral Cr transport by the monocarboxylate transporter 12 (MCT12). Gut microbiota express specific enzymes that can mediate Cr and creatinine breakdown. In hypoxic intestinal epithelial cells, cytosolic CK localizes to apical adherens junctions in complex with the actomyosin cytoskeletal network, providing a conduit for rapid ATP generation during the energy-dependent processes of epithelial junction assembly and barrier restitution