To evaluate the effect of age on sugar transport, we determined the uptake of methyl α-d-glucopyranoside and the abundance of the Na+-d-glucose cotransporter (SGLT1) in jejunal brush-border membrane (BBM) vesicles of 2-day- and 5-wk-old chickens. Methyl α-d-glucopyranoside transport per BBM protein was 40% lower in adults than in newly hatched chickens. This finding was matched by parallel declines in site density of SGLT1, which were detected by Western blot. The immunohistochemical study showed that SGLT1 was exclusively located in the BBM of enterocytes along the entire villus and was absent in the crypt in both age groups, and there was an 11-fold increase in the total absorptive area during development. Northern blot studies of the abundance of SGLT1 mRNA showed similar levels for the groups studied. We conclude that the age-related decline in Na+-dependent hexose transport per unit of BBM protein in the chicken jejunum is due to a reduction in the density of SGLT1 cotransporter and is regulated by a posttranscriptional mechanism.

D-fructose transport was characterized in renal brush-border membrane vesicles (BBMVs) from both spontaneously hypertensive rats (SHR) and normotensive genetic control Wistar-Kyoto (WKY) rats. Kinetic studies indicated that the maximal rate (Vmax) of D-fructose transport was significantly lower in SHR compared with WKY rats. No differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. D-fructose inhibited its own transport, whereas the presence of D-glucose, D-galactose, phlorizin, and cytochalasin B did not inhibit the transport of D-fructose in either animal group. To explain the reduction in D-fructose transport in SHR, the density of the D-fructose transporter, GLUT5, was analyzed by Western blot. GLUT5 levels were lower in SHR, a reduction similar to that of the Vmax. Thus, there appears to be a high-affinity, low-capacity, GLUT5-type fructose carrier in the apical membranes of rat kidney cortex, and the decrease in the Vmax of D-fructose transport in renal BBMVs from hypertensive rats correlates well with a reduction in the expression of GLUT5 protein.

Experimental models of hypertension, such as spontaneously hypertensive rats (SHR), show alterations in cellular sodium transport that affects Na(+)-coupled cotransport processes and has been involved in the pathogenesis of this disease. The objective of the present study was to analyze the kinetic properties of the sodium-dependent glucose transport in the jejunum and ileum of SHR and its genetic control, Wistar-Kyoto (WKY) rats, as well as the regulation of the transporter, SGLT1. In hypertensive rats, the increased systolic blood pressure was accompanied by an enhancement of serum aldosterone levels compared with WKY rats, but no alterations were found in their body weight or serum glucose/insulin levels. The values for d-glucose maximal rate of transport (V(max)) were 42 and 60% lower, respectively, in the jejunum and ileum of SHR than those from WKY rats. On the other hand, the values for the Michaelis constant (K(m)) were similar in both animal groups, as was the diffusive component of transport (K(d)). Immunoblotting and Northern blot analysis revealed the existence of a lower abundance of SGLT1 protein and mRNA in SHR. Moreover, hypertensive rats showed a decrease in the molecular mass of SGLT1 that could not be explained in terms of different glycosylation and/or phosphorylation levels or an alternative splicing in the expression of the protein. These findings demonstrate that SGLT1 is regulated at a transcriptional level in the intestine of hypertensive rats, and suggest that this transporter might participate in the dysregulation of sodium transport observed in hypertension.

Na(+)-dependent D-glucose and D-galactose transport were studied in brush-border membrane vesicles (BBMVs) from kidney cortex isolated from both spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto (WKY) rats. Initial rates and accumulation ratios of Na(+)-dependent D-glucose and D-galactose transport were significantly lower in SHR compared with WKY, the observed decreases being similar for both substrates. To explain the reduction in sugar transport by renal BBMVs, the density of Na(+)-dependent sugar cotransporters was studied in BBMVs from kidney cortex isolated from SHR and WKY rats. Phlorizin-specific binding and Western blot analysis indicated a reduction in the density of the cotransporters in SHR relative to WKY rats. This reduction was similar to those found for the initial rates and accumulation ratios for D-glucose and D-galactose in SHR. Na+ uptake, studied using 22Na+, was significantly increased in SHR, so the observed reduction in sugar transport could be due to disruption of the Na+ gradient between renal BBMVs in SHR. Furthermore, a significant decrease in the activity of Na(+)-K(+)-ATPase was observed in SHR. In conclusion, changes in the density of the Na(+)-dependent sugar cotransporter and in the Na+ gradient across the brush-border membranes might be involved in the observed reduction in sugar transport by renal BBMVs from SHR.

In the chicken intestine, the reduction in Na+ intake led to a decrease in the transport of α-methyl-d-glucoside in the ileum (reduction of 42%) and in the rectum (51%). These reductions were reversed within 24 h after resalination and were inversely correlated to the changes in aldosterone plasma concentration. The reduction in intestinal hexose transport in the low Na+-fed animals was due to a decrease in the number of Na+-dependent d-glucose cotransporters (SGLT1) in the rectum (46%) and in the ileum (38%). Northern blot analysis showed that specific SGLT1 mRNA was expressed in the jejunum, ileum, and rectum. The amount of SGLT1 mRNA was the same in all intestinal regions and was not affected by Na+ intake, supporting the view that the effects of dietary Na+ on intestinal hexose transport involve posttranscriptional regulation of SGLT1. This study suggests that changes in SGLT1 expression may be involved in the homeostasis of Na+.