Aliases: IBAT, ISBAT, ISBT
Gene name: Solute carrier family 10 member 2 (Slc10a2)
The rat ileal sodium-dependent bile acid (BA) cotransporter was cloned and expressed in Xenopus oocytes in 1995 . The human and rat orthologs share 83% amino acid homology. Expression of rAsbt has been detected on the apical surface of ileal enterocytes, renal proximal tubular cells and cholangiocytes, similar to the human protein [2-4]. An alternatively spliced variant named t-Asbt is localized to the basolateral domain of cholangiocytes, ileal enterocytes, and renal tubular epithelial cells. This truncated variant exhibited activity as a taurocholic acid efflux carrier in in vitro experiments in Xenopus oocytes . Regulation of both variants by BAs was investigated by several groups, but no consensus was achieved as to whether a negative feedback regulatory mechanism similar to mice and humans exists [6-9].
Studying the effect of Asbt/ASBT inhibitors in animal models for BA-related diseases can help to find novel approaches for disease control. In Zucker diabetic obese rats, oral administration of an Asbt inhibitor significantly decreased glucose levels and prevented the drop of insulin levels in a dose-dependent manner . In the Zucker rat model of obesity, Asbt activity was significantly increased in intact ileal villus cells compared to cells from wild type rat. Western blot studies suggested that the increase in transporter activity was a consequence of increased expression of the Asbt protein .
Enhancing intestinal absorption through BA-derived prodrugs that target Asbt/ASBT is a relatively new strategy. A cholyl-insulin formulation was shown to be absorbed from rat small intestine, and the absorption was specific to the ileum and could be blocked by taurocholate . By orally administering deoxycholic acid-modified chitosan nanoparticles loaded with insulin, a bioavailability of 16% was achieved in type I diabetic rats. Intravital two-photon microscopy revealed that the transport of the nanoparticles into the intestinal villi was mediated by Asbt .
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