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Apical GLUT2 and Ca v 1.3: regulation of rat intestinal glucose and calcium absorption
Author(s) -
Morgan Emma L.,
Mace Oliver J.,
Affleck Julie,
Kellett George L.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.124768
Subject(s) - glut2 , phloretin , verapamil , chemistry , apical membrane , glucose transporter , medicine , nifedipine , calcium , endocrinology , biophysics , biochemistry , biology , membrane , insulin , organic chemistry
We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2 in the apical membrane by a PKC βII‐dependent mechanism. Since PKC βII requires Ca 2+ and glucose is depolarizing, we have investigated whether glucose absorption is regulated by the entry of dietary Ca 2+ through Ca v 1.3 in the apical membrane. When rat jejunum was perfused with 75 m m glucose, Ca 2+ ‐deplete conditions, or perfusion with the L‐type antagonists nifedipine and verapamil strongly diminished the phloretin‐sensitive apical GLUT2, but not the phloretin‐insensitive SGLT1 component of glucose absorption. Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level. Inhibition of apical GLUT2 absorption coincided with inhibition of unidirectional 45 Ca 2+ entry by nifedipine and verapamil. At 10 m m luminal Ca 2+ , 45 Ca 2+ absorption in the presence of 75 m m glucose was 2‐ to 3‐fold that in the presence of 75 m m mannitol. The glucose‐induced component was SGLT1‐dependent and nifedipine‐sensitive. RT‐PCR revealed the presence of Ca v β 3 in jejunal mucosa; Western blotting and immunocytochemistry localized Ca v β 3 to the apical membrane, together with Ca v 1.3. We conclude that in times of dietary sufficiency Ca v 1.3 may mediate a significant pathway of glucose‐stimulated Ca 2+ entry into the body and that luminal supply of Ca 2+ is necessary for GLUT2‐mediated glucose absorption. The integration of glucose and Ca 2+ absorption represents a complex nutrient‐sensing system, which allows both absorptive pathways to be regulated rapidly and precisely to match dietary intake.