BAS作为降糖药——降糖机制、临床疗效及应用前景

Bile Acid Sequestrants:Glucose-lowering mechanisms,treatment effects and application prospects

胆汁酸(Bile acids)用于治疗血脂异常已超过25年,其与不可吸收的树脂在肠腔内结合形成胆汁酸螯合物BAS(考来烯胺、考来维仑、colestimide、考来替泊)调节胆汁酸代谢,BAS经便排泄,并经由肠肝循环重吸收。胆汁酸可通过影响核受体FXR和TGR5调节肝糖代谢、外周胰岛素敏感性和能量代谢等。临床研究表明胆汁酸能够降低LDL,有利于预防冠心病。另外,2008年已证明BAS盐酸考来维仑(colesevelam HCl)联合饮食控制和运动疗法可改善T2DM血糖控制。最早Garg A等1994年一项为期6周的随机双盲交叉对照证明,盐酸考来烯胺降低血糖和HbA1c,随后2008年Goldberg RB等对胰岛素治疗DM控制不满意的患者、Fonseca等对二甲双胍或磺脲类药物(SUs)治疗DM控制不满意的患者研究发现,盐酸考来维仑均可改善这些患者的血糖控制情况。

Bile acids have 13een used for over 25 years for the therapy of dyslipidemia. Nonabsorbable resins could chelate bile acids in the intestinal lumen as Bile Acids Sequestrant（BAS, colestyramine, colesevelam, colestimide, colestipol）to regulate biles acids metabolism, decreasing their enterohepatic recirculatiorL BAS are excreted in the feces and only a part of BAS was re_absorbed into the entemhepatic circulation. Bile acids have been reported to regulate hepatic glucose metabolism, peripheral insulin sensitivity and energy metabolism by FXR- and TGRS-dependent pathways. Several clinical studies have indicated the benefit of their cholesterol lowering effect for the prevention of coronary heart disease Additionally, colesevelam hydrochloride （HC1） was approved in 2008 as an adjunct to diet and exercise to improve glyeemic control in adults with T2DM. The first observation for such an effect of BAS came from a randomized, double-blind, crossover study in 1994 by Garg A, et al. in which eholestyramine was administered to T2DM patients for 6 weeks and resulted in reduction of plasma glucose levels and a tendency to lower glycosylated hemoglobin（HbA1 e） levels. Subsequent studies confirmed colesevelam HC1 improved glycemic control in patients with T2DM who were not adequately controlled by insulin, sulfonylurea, or metformin therapy. Here we translated essential parts of some reports on BAS in the following artide.