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

Abstract

Cui, Xue-Lin, Anna M. Schlesier, Elda L. Fisher, Carla Cerqueira, and Ronaldo P. Ferraris. Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway. Am J Physiol Gastrointest Liver Physiol 288: G1310 -G1320, 2005. First published February 3, 2005 doi:10.1152/ajpgi.00550.2004.-Expression of rat glucose transporter-5 (GLUT5) is tightly regulated during development. Expression and activity are low throughout the suckling and weaning stages, but perfusion of the small intestinal lumen with fructose solutions during weaning precociously enhances GLUT5 activity and expression. Little is known, however, about the signal transduction pathways involved in the substrate-induced precocious GLUT5 development. We found that wortmannin and LY-294002, inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) specifically inhibited the increase in fructose uptake rate and brushborder GLUT5 protein abundance but not GLUT5 mRNA abundance. Perfusion of EGF, an activator of PI3-kinase, also resulted in a marked wortmannin-inhibitable increase in fructose uptake. Perfusion of fructose for 4 h increased cytosolic immunostaining of phosphatidylinositol-3,4,5-triphosphate (PIP 3), the primary product of PI3-kinase, mainly in the mid-to upper-villus regions in which the brush-border membrane also stained strongly with GLUT5. Perfusion of glucose for 4 h had little effect on fructose or glucose uptake and PIP 3 or GLUT5 staining. SH-5, an Akt inhibitor, prevented the increase in fructose uptake and GLUT5 protein induced by fructose solutions, and had no effect on glucose uptake. The PI3-kinase/Akt signaling pathway may be involved in the synthesis and/or recruitment to the brush border of GLUT5 transporters by luminal fructose in the small intestine of weaning rats. Increases in fructose transport during the critical weaning period when rats are shifting to a new diet may be modulated by several signaling pathways whose cross talk during development still needs to be elucidated. development; glucose; intestine; epidermal growth factor; mucosa BECAUSE OF DRAMATIC INCREASES in consumption of soft drinks and fruit juices, per capita consumption of fructose in the United States has increased by 10 times in 30 yr to almost 60 g fructose per day (4, 39). Paralleling this remarkable increase in fructose consumption is an alarming increase in incidence of obesity and in prevalence of type II diabetes (4,14). What makes this correlation disturbing is that per capita fructose consumption in very young children has increased faster than that of the general population and in the 1980s was already ϳ30 -40 g fructose per day representing 10% of their energy intake (39). The top 10th percentile of subjects in all age groups typically consume approximately two times more fructose, exposing this particular age group (1-6 yr of age) to potential metabolic derangements caused by excessive fructose consumption. There are very few studies on physiological adaptations to excessive fructose consumpti...

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

“…Furthermore, it is known that glucocorticoid hormones (Si, Slc2a5 and Treh) and thyroid hormones (Si, Slc2a5 and Treh) enhance intestinal gene expressions during the transient suckling-weaning period (4,5,13,32). In addition, the expressions of these genes are known to be upregulated by dietary carbohydrate (9,10,51,52). Therefore, the changes in gene expression between days 13 and 27 detected in our microarray analysis may be regulated by these hormones and dietary factors.…”

“…Agbemafle et al ( 8 ) examined glucocorticoid hormoneresponsive genes during the suckling period by microarray analysis. Cui et al ( 9,10 ) showed that fructoseresponsive genes, such as glucose-6-phosphatase, fructose-1, 6-bisphosphatase and the PI3 kinase cascade, were upregulated by fructose perfusion in weaning rats. However, these observations only focused on glucocorticoid hormone-or fructose-responsive genes, and the detailed changes in gene expression in the rat small intestine during the transient suckling-weaning period remain unknown.…”

Glucose and Lipid Transporters Roles in Type 2 Diabetes

“…In type 2 diabetes mellitus (T2DM) patients, SGLT1 was found to be increasingly expressed in certain studies. 1,5,24 In addition, increased glucose uptake in cardiomyocytes following stimulation caused by insulin and leptin signaling illustrates how insulin and leptin may be partly responsible for either SGLT1 expression or translocation to the membrane, as well as increased glucose uptake activity [6,7]. Two laboratories reported partially contradicting results in SGLT1 kidney tissue expression, with the first [8] identifying that SGLT1 expression in T2DM patients is higher than in control patients and the second reporting the same or lower expression of SGLT1/2 and GLUT1/2 when the T2DM patients were compared to the control patients.…”

“…Both genes ABCA1 and ABCG1 role in cholesterol efflux in macrophages to high density lipoproteins are critical in reducing risk of heart disease (Table 3). Furthermore, studies have linked mutations and defects in these genes to T2DM patients, signaling the crucial role of the genes in patients affected by T2DM because of the risk caused by their dysfunction [23,24].…”

“…Stimulating LXR increases the expression of ABCA1 and ABCG1 by increasing transcription rates, therefore increasing the cholesterol efflux function of the transporters. It is noted that oxysterols act as agonists for LXR, and other synthetic agonists have proven effective [24]. ABCG1 expression was found to be reduced in T2DM patients [25].…”