Staels Bart
Universite Lille Nord de France, Inserm U545, UDSL, Lille, France.
Postgrad Med. 2009 May;121(3 Suppl 1):25-30. doi: 10.3810/pgm.2009.05.suppl53.290.
Clinical evidence has demonstrated that bile acid sequestrants reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). This effect has been confirmed in multiple double-blind, placebo-controlled clinical studies with the bile acid sequestrant colesevelam hydrochloride (HCl). Colesevelam HCl was approved by the US Food and Drug Administration in January 2008 as an adjunctive therapy for patients with T2DM to improve glycemic control. However, the mechanism of action for the glucose-lowering effect of bile acid sequestrants is unclear. Bile acid sequestrants are nonsystemic pharmacological agents that bind bile acids in the gastrointestinal tract, thereby diverting bile acids from the enterohepatic circulation. This, in turn, upregulates bile acid synthesis (via cholesterol 7-alpha-hydroxylase), which utilizes cholesterol, resulting in reduced low-density lipoprotein cholesterol levels. Recent research has revealed that bile acids are tightly controlled signaling molecules that have metabolic effects beyond their primary role in bile to aid in the digestion of lipids and fat. Bile acids signal via various membrane and nuclear receptors. Therefore, bile acid sequestrants may exert glycemic effects by altering the interaction of these bile acid pathways. This article reviews the role for bile acids in glucose regulation and discusses the potential mechanism(s) of action for the glycemic effects of bile acid sequestrants.
临床证据表明，胆汁酸螯合剂可降低2型糖尿病（T2DM）患者的血糖水平。在多项使用胆汁酸螯合剂盐酸考来维仑的双盲、安慰剂对照临床研究中，这一效果得到了证实。盐酸考来维仑于2008年1月被美国食品药品监督管理局批准作为T2DM患者的辅助治疗药物，以改善血糖控制。然而，胆汁酸螯合剂降血糖作用的机制尚不清楚。胆汁酸螯合剂是一种非全身性药理剂，它在胃肠道中与胆汁酸结合，从而使胆汁酸从肠肝循环中转移出来。这反过来又上调了胆汁酸的合成（通过胆固醇7-α-羟化酶），该过程利用胆固醇，导致低密度脂蛋白胆固醇水平降低。最近的研究表明，胆汁酸是受到严格调控的信号分子，除了在胆汁中帮助消化脂质和脂肪的主要作用外，还具有代谢作用。胆汁酸通过各种膜受体和核受体发出信号。因此，胆汁酸螯合剂可能通过改变这些胆汁酸途径的相互作用来发挥血糖效应。本文综述了胆汁酸在血糖调节中的作用，并讨论了胆汁酸螯合剂血糖效应的潜在作用机制。
