Figure 1.

Nutrient-sensing mechanisms of intestinal hormone release from EECs. Peptides and amino acids, carbohydrates, fats, and bile salts can elicit responses either apically (top) or basolaterally (bottom). Peptides and amino acids are transported into EECs by PEPT1 (with H⁺) and B(0)AT (with Na⁺), respectively, whereas glucose is co-transported along with Na⁺ by SGLT1. This process causes membrane depolarisation and activates VGCCs, increasing intracellular calcium and therefore releasing gut hormones into the system. The same transporters are also located in the enterocytes so amino acids and glucose can be absorbed and reach the basolateral surface where different GPCRs are expressed, including CASR, GPR142, GPR93, GPRC6A and TAS1R2/3. Fatty acid and bile acid transporters are involved in their uptake across the brush border. Basolateral LCFAs can stimulate Gαq-coupled GPCRs FFAR1 and FFAR4, whereas SCFA can activate Gαi-coupled FFAR3, Gαi/q FFAR2 and Gαs OR51E1/2. Monoacylglycerols activate Gαs-coupled GPR119, provoking gut hormone secretion through increasing AC activity and cAMP levels. Abbreviations: peptide transporter 1 (PEPT1), neutral amino acid transporter 1 (B(0)AT), sodium-coupled glucose cotransporter 1 (SGLT1), cluster of differentiation (CD36), voltage-gated calcium channels (VGCCs), endoplasmic reticulum (ER), cyclic adenosine monophosphate (cAMP), adenylyl cyclase (AC), amino acids (AAs), long-chain fatty acids (LCFAs), short-chain fatty acids (SCFAs), oleoylethanolamide (OEA), 2-acylglycerol (2-AG), G-protein-coupled receptor (GPCR), calcium sensing receptor (CASR), transient receptor potential cation channel subfamily M member 5 (TRPM5), free fatty acid receptor 1-4 (FFAR1-4), G-protein-coupled bile acid receptor 1 (GPBAR1).