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

摘要

There is increasing evidence that locally produced angiotensin AII (AII) regulates the function of many tissues, but the involvement of enterocyte-derived AII 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 AII on SGLT1-dependent glucose transport across the brush border membrane (BBM). Gene and protein expression of angiotensinogen, ACE, and AT_1 and AT_2 receptors were studied in jejunal and ileal enterocytes using immunocytochemistry, Western blotting and RT-PCR. Mucosal uptake of d-[~(14)C] glucose by everted intestinal sleeves before and after addition of AII (0-100 nM) to the mucosal buffer was measured in the presence or absence of the AT_1 receptor antagonist losartan (1 mum). Immunocytochemistry revealed the expression of angiotensinogen, ACE, and AT_1 and AT_2 receptors in enterocytes; immunoreactivity of AT_1 receptor and angiotensinogen proteins was especiallypronounced atthe BBM. Expression of angiotensinogen and AT_1 and AT_2 receptors, but not ACE, was greater in the ileum than the jejunum. Addition of AII to mucosal buffer inhibited phlorizin-sensitive (SGLT_1-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 AII on glucose uptake. AII 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 AII suggest that AII secretion exerts autocrine control of intestinal glucose transport.