Lumenal adenosine and AMP rapidly increase glucose transport by intact small intestine.
Adenosine modulates the intestinal functions of secretion, motility, and immunity, yet little is known about the regulation of nutrient absorption. Therefore, we measured the carrier-mediated uptake of tracer D-[(14)C]glucose (2 microM) by everted sleeves of the mouse intestine after a lumenal exposure to adenosine and a disodium salt of AMP. Rates of glucose uptake by intact tissues increased almost twofold after a 7-min exposure to 5 mM adenosine (a physiological dose). The response was slightly more pronounced for AMP and could be induced by forskolin. The response to adenosine was blocked by theophylline and the A(2) receptor antagonist 3,7-dimethyl-1-proparglyxanthine but not by the A(1) receptor antagonist 8-phenyltheophylline. Glucose uptake by control and AMP-stimulated tissues was inhibited by phloridzin, implying that sodium-dependent glucose transporter 1 (SGLT1) is the responsive transporter, but the involvement of glucose transporter 2 (GLUT2) cannot be excluded. Of clinical relevance, AMP accelerated the systemic availability of 3-O-methylglucose after an oral administration to mice. Our results indicate that adenosine causes a rapid increase in carrier-mediated glucose uptake that is of clinical relevance and acts via receptors linked to a signaling pathway that involves intracellular cAMP production.
Kimura
Yasuhiro
Y
Dept. of Biological Sciences, Mississippi State University, MS 39762, USA.
Turner
Jerrold R
JR
Braasch
Dwaine A
DA
Buddington
Randal K
RK
D019325:3-O-Methylglucose / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058915:Purinergic P1 Receptor Antagonists; D015398:Signal Transduction; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D013268:Stimulation, Chemical; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D019325:3-O-Methylglucose; D005576:Colforsin; D000249:Adenosine Monophosphate; C057837:3,7-dimethyl-1-propargylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D005947:Glucose; D000241:Adenosine; D013805:Theobromine