An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine

Abstract

T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/α-gustducin to activate PLC β2 and PKC βII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca 2+ -dependent reciprocal relationship between the H + /oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC βII, respectively. Addition of l-glutamate or sucralose to a perfusate containing low glucose (20 mm) each activated PKC βII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide l-Phe( S)-l-Ala (1 mm), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mm) exerted similar effects. l-Glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and α-gustducin. We conclude that l-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC βII. These data suggest the existence of a wider Ca 2+ and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC βII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by l-glutamate. The network may control energy supply.

Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery

“…In the pancreas, sweet taste receptor activation has been reported to potentiate glucose-stimulated insulin secretion (34,49). In the intestine, this receptor has been implicated in glucose absorption, whereas ␣-gustducin has been shown to be critical for glucose-stimulated incretin secretion (31,(41)(42)(43) from enteroendocrine cells. Mice lacking ␣-gustducin exhibit decreased expression of the Na ϩ -glucose cotransporter SGLT1 in the intestine, elevated blood glucose levels, a delayed rise in plasma insulin levels, and a diminished incretin response after a glucose challenge compared with controls (31,43).…”

Structure of, and functional insight into the GLUT family of membrane transporters

“…[158][159][160][161][162][163] In contrast, stress, a high-fat diet, and glucocorticoids inhibit GLUT2 trafficking to the brush border membrane. [164][165][166] Most recently, subcellular localization studies using live cell imaging demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, which is partially recovered in Rab11A-positive recycling endosomes.…”

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

“…Supplementation of the diet with sucralose increases the expression of SGLT1 in the enterocytes of wild-type mice, but not in mice deficient in T1R3 or a-gustducin (4) . The presence of sucralose enhances insertion of GLUT2 into the apical region of the enterocytes, and thus, stimulates glucose absorption in rats (7,8) . For example, sucralose administration doubled the level of GLUT2 protein…”