Ontogenic development of lamb intestinal sodium‐glucose co‐transporter is regulated by diet.

Abstract

1. The ontogenic development of the intestinal Na(+)‐glucose co‐transporter was measured in lambs as a function of diet. Transport activity was assayed in brush‐border membrane vesicles and the expression of transport protein in the brush‐border membrane determined by Western analysis. 2. Na(+)‐dependent D‐glucose transport increased to a maximum (300‐700 pmol mg‐1 s‐1) within the first 2 weeks of birth and then declined to negligible amounts (less than 10 pmol mg‐1 s‐1) over the next 8 weeks. There was no further change over the next 2‐3 years. Early changes were associated with modifications in both the maximum velocity Vmax for transport and expression of carrier protein in the brush‐border plasma membrane. 3. Maintaining lambs on a milk replacer diet beyond the normal weaning period prevented the normal decline in the expression of Na(+)‐glucose co‐transport. At 5 weeks the transport rate was 433 +/‐ 150 pmol mg‐1 s‐1 in lambs maintained on milk replacer, but only 79 +/‐ 40 pmol mg‐1 s‐1 in normally reared control lambs. 4. Infusing the proximal intestine of 2‐ to 3‐year‐old sheep with 30 mM‐D‐glucose for four days increased the rate of transport 40‐ to 80‐fold above that found in control animals perfused with mannitol. A similar but smaller increase was observed in one animal perfused with the non‐metabolizable sugar alpha‐methyl‐D‐glucopyranoside. The induced increase in glucose transport was correlated with the expression of the co‐transporter protein in the brush‐border plasma membrane. 5. It is concluded that the age‐related decline in Na(+)‐glucose co‐transport in the sheep intestine is directly due to the decrease in D‐glucose (and D‐galactose) reaching the small intestine after development of the rumen. These results further suggest that luminal sugar substrates for the co‐transporter promote both the maintenance and the up‐regulation of the brush‐border transport protein and it is the intact sugar itself which controls gene expression during enterocyte maturation.