Involvement of an enterocyte renin-angiotensin system in the local control of SGLT1-dependent glucose uptake across the rat small intestinal brush border membrane

There is increasing evidence that locally produced angiotensin All (All) regulates the function of many tissues, but the involvement of enterocyte-derived All in the control of intestinal transport is unknown. This study examined whether there is a local renin-angiotensin system (RAS) in rat villus enterocytes and assessed the effects of All on SGLT1-dependent glucose transport across the brush border membrane (BBM). Gene and protein expression of angiotensinogen, ACE, and AT, and AT2 receptors were studied in jejunal and ileal enterocytes using immunocytochemistry, W stern blotting and RT-PCR. Mucosal uptake Of D-[(14)C] glucose by everted intestinal sleeves before and after addition of All (0-100 nM) to the mucosal buffer was measured in the presence or absence of the AT, receptor antagonist losartan (1 mu M). Immunocytochemistry revealed the expression of angiotensinogen, ACE, and AT, and AT2 receptors in enterocytes; immurtoreactivity of AT, receptor and angiotensinogen proteins was especially pronounced at the BBM. Expression of angiotensinogen and AT(1) and AT(2) receptors,but not ACE, was greater in the ileurn than the jejunum. Addition of All to mucosal buffer inhibited phlorizin-sensitive (SGU1-dependent) jejunal glucose uptake in a rapid and dose-dependent manner and reduced the expression of SGLT1 at the BBM. Losartan attenuated the inhibitory action of All on glucose uptake. All did not affect jejunal uptake Of L-leucine. The detection of RAS components at the enterocyte BBM, and the rapid inhibition of SGLT1 -dependent glucose uptake by luminal All suggest that All secretion exerts autocrine control of intestinal glucose transport.