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

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Published copy (DOI)

Author(s)

  • Oliver J. Mace
  • Norma Lister
  • Emma Morgan
  • Emma Shepherd
  • Julie Affleck
  • Philip Helliwell
  • John R. Bronk
  • George L. Kellett
  • David Meredith
  • Richard Boyd
  • Myrtani Pieri
  • Pat D. Bailey
  • Rachel Pettcrew
  • David Foley

Department/unit(s)

Publication details

JournalJournal of Physiology
DatePublished - 1 Jan 2009
Issue number1
Volume587
Number of pages16
Pages (from-to)195-210
Original languageEnglish

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/alpha-gustducin to activate PLC beta 2 and PKC beta II. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca2+-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 beta II, respectively. Addition of l-glutamate or sucralose to a perfusate containing low glucose (20 mm) each activated PKC beta II and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide l-Phe(Psi 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 alpha-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 beta II. These data suggest the existence of a wider Ca2+ and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC beta II and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by l-glutamate. The network may control energy supply.

    Research areas

  • PROTEIN-KINASE-C, OLIGOPEPTIDE TRANSPORTER PEPT-1, BRUSH-BORDER MEMBRANE, CELL LINE CACO-2, PEPTIDE TRANSPORTER, SUGAR ABSORPTION, APICAL GLUT2, GLUCOSE-ABSORPTION, EPITHELIAL-CELLS, H+/PEPTIDE COTRANSPORTER

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