Intrahepatic bile ducts transport water in response to absorbed glucose

Abstract

The physiological relevance of the absorption of glucose from bile by cholangiocytes remains unclear. The aim of this study was to test the hypothesis that absorbed glucose drives aquaporin (AQP)-mediated water transport by biliary epithelia and is thus involved in ductal bile formation. Glucose absorption and water transport by biliary epithelia were studied in vitro by microperfusing intrahepatic bile duct units (IBDUs) isolated from rat liver. In a separate set of in vivo experiments, bile flow and absorption of biliary glucose were measured after intraportal infusion of D-glucose or phlorizin. IBDUs absorbed D-glucose in a dose- and phlorizin-dependent manner with an absorption maximum of 92.8 +/- 6.2 pmol. min(-1). mm(-1). Absorption of D-glucose by microperfused IBDUs resulted in an increase of water absorption (J(v) = 3-10 nl. min(-1). mm(-1), P(f) = 40 x 10(-3) cm/sec). Glucose-driven water absorption by IBDUs was inhibited by HgCl(2), suggesting that water passively follows absorbed D-glucose mainly transcellularly via mercury-sensitive AQPs. In vivo studies showed that as the amount of absorbed biliary glucose increased after intraportal infusion of D-glucose, bile flow decreased. In contrast, as the absorption of biliary glucose decreased after phlorizin, bile flow increased. Results support the hypothesis that the physiological significance of the absorption of biliary glucose by cholangiocytes is likely related to regulation of ductal bile formation.

Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation

“…It is tempting to speculate that this type of mechanism might operate physiologically not only in the crypts of the small intestine, but also in the intrahepatic bile ducts and in distal portions of the nephron and renal calices. Supporting this assumption, glucose absorption from the bile by cholangiocytes was already reported and proposed to be an important factor to drive water reabsorption (Guzelian and Boyer 1974;Masyuk et al 2002). Indeed, rather low glucose concentrations ranging from 50 to 300 mg/l were measured in rat bile (Guzelian and Boyer 1974).…”

Localizations of Na+-d-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart

“…In rat, it has been shown that glucose enters the bile passively from hepatocytes and is reabsorbed in bile ducts by phlorizin-inhibitable Na + -D-glucose cotransport [9,17]. Employing an ex vivo study with bile duct units isolated from rat liver, it has been shown that the secondary active reabsorption of glucose in the bile ducts provides the osmotic driving force for water reabsorption via aquaporins [31]. This mechanism may explain the observation that the bile flow decreases in diabetic rats [8] and may contribute to cholestasis during diabetes.…”

Expressions of hepatic genes, especially IGF-binding protein-1, correlating with serum corticosterone in microarray analysis

“…The protein product of Clic4, a mitochondrial chloride channel protein, has been implicated in apoptotic response to DNA damage (FernandezSalas et al 2002). The water channel protein aquaporin 2 apparently is not expressed in rat liver (Umenishi et al 1996, Huebert et al 2002, but has not been studied in mice; it may have a role in glucose-driven water transport in liver (Masyuk et al 2002).…”