REGULATION OF THE OVINE INTESTINAL NA-RNA ABUNDANCE( GLUCOSE COTRANSPORTER (SGLT1) IS DISSOCIATED FROM MESSENGER)

We have investigated the mechanisms of regulation of the Na+/glucose c o-transporter (SGLT1) in a ruminant animal, which is an exceptional mo del system for studying intestinal glucose transport. Pre-ruminant lam bs absorb glucose, produced by hydrolysis of the milk sugar lactose, i n the intestine via apical SGLT1 and basolateral facilitative glucose transporters (GLUT2). Weaning coincides with the development of the ru men, and consequently the amount of hexoses reaching the small intesti ne of the ruminant sheep is undetectable. During development, SGLT1 ac tivity and abundance in intestinal brush-border membranes decreased by over 200-fold, and either maintaining lambs on a milk replacer diet o r infusing sheep intestine with D-glucose restored co-transporter acti vity and expression. We have measured ovine intestinal SGLT1 mRNA leve ls during development, with changes in diet and after direct infusion of D-glucose or methyl alpha-D-glucopyranoside into the intestinal lum en, in order to determine the level of regulation. During development, mRNA levels decreased only 4-fold. Lambs maintained on a milk replace r diet showed no change in mRNA levels relative to age-matched control s. Finally, upon infusion of the intestine of the ruminant sheep with sugars, D-glucose infusion increased SGLT1 mRNA, but only by 2-fold, c ompared with a 60-90-fold increase in co-transporter number and activi ty. Since the change in Na+-dependent glucose transport activity is co rrelated with SGLT1 protein abundance, and since changes in mRNA level s do not account for the dramatic changes in protein abundance, we con clude that the principal level of SGLT1 regulation by luminal sugar is translational or post-translational.