Hepatic expression and cellular distribution of the glucose transporter family

Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required.

Psoraleae induces hepatotoxicity by affecting bile acid balance

Buguzhi(Psoraleae fructus),the seed of Psoralea corylifolia Linn,is used to treat osteoporosis,nephritis,vitiligo and other diseases.However,long-term routine or overdose of Psoraleae fructus may lead to hepatotoxicity and become a major obstacle of its clinical usage.Psoralen was a key active component of Psoraleae fructus,and a main cause of Psoraleae fructus toxicity.This research was to investigate the hepatotoxicity of psoralen and whether it’s related with bile acid imbalance.Methods:C57BL/6 mice were randomly divided into 4 groups(n=10).Psoralen(20 mg/kg,40 mg/kg and 80 mg/kg)was administrated intragastrically once every day and control group with equivalent water until 4 weeks.Results:The results showed that psoralen caused an increase in liver coefficient and the injury of hepatocytes microstructure of mice.It also inhibited cell viability of HepG2 cells.Mice treated with psoralen exerted liver total bile acid increased while serum total bile acid decreased,which indicated that psoralen-induced liver injury may partly associate with cholestasis.For further study of liver transporters,high dose of psoralen inhibited the expression of some important hepatic efflux transporters(including BSEP,p-gp and ABCG5)in vivo and in vitro.Conclusion:We provide evidence for the first time that psoralen may induce cholestatic hepatotoxicity for the bile acid retention by inhibition on bile acid export pumps.

Total Flavonoids from Flowers of Abelmoschus manihot for Amelioration of α-naphthylisothiocyanate-induced Cholestasis by Regulating Expression of Transporters

Objective To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot（TFA） against α-naphthylisothiocyanate（ANIT）-induced cholestasis. Methods The hepatoprotective activities of TFA（125, 250 and 500 mg/kg） were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, total bilirubin（TBIL）, total bile acid（TBA）, and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic m RNA and protein levels of transports, multidrug resistance-associated protein 2（MRP2）, bile salt export pump（BSEP）, and Na＋-taurocholate cotransporting polypeptide（NTCP） were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and m RNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.