Cyclic AMP Stimulates Fructose Transport in Neonatal Rat Small Intestine

Abstract

Intestinal fructose transporter (GLUT5) expression normally increases significantly after completion of weaning in neonatal rats. Increases in GLUT5 mRNA, protein, and activity can be induced in early weaning pups by precocious consumption of dietary fructose or by perfusion of the small intestine with fructose solutions. Little is known about the signal transduction pathway of the dietary fructose-mediated increase in GLUT5 expression during early intestinal development. Recent microarray results indicate that key gluconeogenic enzymes modulated by cAMP are markedly upregulated by fructose perfusion; hence, we tested the hypothesis that cAMP plays an important role in regulating intestinal fructose absorption by simultaneously perfusing adenylyl cyclase, phosphodiesterase, or protein kinase A (PKA) inhibitors along with fructose. Intestinal fructose uptake rates increased by 100% in rat pups perfused with 8-bromo-cAMP. Simultaneous fructose and dideoxyadenosine (DDA; inhibitor of adenylyl cyclase) perfusion completely inhibited increases in fructose uptake rate induced by perfusion with fructose alone. Fructose perfusion increased intestinal mucosal cAMP concentrations by 27%, but simultaneous perfusion of fructose and DDA inhibited the fructose-induced increase in cAMP. However, GLUT5 and sodium-glucose cotransporter (SGLT1) mRNA abundance and glucose transport rates were each not significantly affected by 8-bromo-cAMP and DDA. Moreover, simultaneous perfusion of the small intestine with fructose and PKA inhibitor or N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamid. 2HCl, both inhibitors of PKA, did not prevent the fructose-induced increases in GLUT5 mRNA abundance and fructose uptake rate. Cyclic AMP appears to modulate fructose transport without affecting GLUT5 mRNA abundance, and without involving PKA.

Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway

“…It turns out that the cAMPstimulated increases in taurocholate transport can be prevented by PI3-kinase and Akt inhibitors and involves the translocation of NTCP transporters to the plasma membrane of hepatocytes (35). Although we did not use PI3-kinase and PKB inhibitors in our cAMP experiments (8), it is interesting to note that the fructose-induced fructose transport in rat neonates that can be inhibited by dideoxyadenosine (an inhibitor of adenylyl cyclase) in previous work has also been shown to be inhibited by PI3-kinase and Akt inhibitors. 3).…”

Fructose transporter Glut5 expression in clear renal cell carcinoma

“…Fructose is transported passively across membranes by a member of the facilitative glucose transporter (GLUT) family, named GLUT5 (60)(61)(62)(63)(64) and it is the sole transporter specific for fructose with no ability to transport glucose or galactose. The low intracellular fructose concentration is possible because fructose is metabolized and significantly contributes to glycogenolysis in muscle or lipogenesis in adipocytes (63,65).…”

“…FBPase activity is indirectly regulated by cAMP, which increases in vivo in the kidney epithelia exposed to fructose compared with those exposed to glucose. It has been demonstrated in vivo that cAMP modulates fructose transport induced by fructose without affecting GLUT5 mRNA abundance (65), whereas in vitro, cAMP affects GLUT5 mRNA expression levels and is involved in GLUT5 regulation in kidney epithelia (67)(68)(69)(70).…”

Regulation of the fructose transporter GLUT5 in health and disease

“…This increase in GLUT5 expression and activity can be advanced developmentally in younger, weaning pups. Between 14 and 28 days of age, GLUT5 is dramatically stimulated by early introduction of dietary fructose or by gavage feeding fructose solutions into the gastric lumen (35,42,45,75,112,139). At this age range, the nutritional regulation of GLUT5 by fructose is clearly genomic (75) and requires the presence of fructose in intestinal lumen (140).…”