Haider Dominik G, Mittermayer Friedrich, Schaller Georg, Artwohl Michaela, Baumgartner-Parzer Sabina M, Prager Gerhard, Roden Michael, Wolzt Michael
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E885-90. doi: 10.1152/ajpendo.00109.2006. Epub 2006 May 30.
The detrimental effect of elevated free fatty acids (FFAs) on insulin sensitivity can be improved by thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus. It is unknown whether this salutary action of TZD is associated with altered release of the insulin-mimetic adipocytokine visfatin. In this study, we investigated whether visfatin concentrations are altered by FFA and TZD treatment. In a randomized, double-blind, placebo-controlled, parallel-group study 16 healthy volunteers received an infusion of triglycerides/heparin to increase plasma FFA after 3 wk of treatment with rosiglitazone (8 mg/day, n = 8) or placebo (n = 8), and circulating plasma visfatin was measured. As a corollary, human adipocytes were incubated with synthetic fatty acids and rosiglitazone to assess visfatin release in vitro. The results were that rosiglitazone treatment increased systemic plasma visfatin concentrations from 0.6 +/- 0.1 to 1.7 +/- 0.2 ng/ml (P < 0.01). Lipid infusion caused a marked elevation of plasma FFA but had no effect on circulating visfatin in controls. In contrast, elevated visfatin concentrations in subjects receiving rosiglitazone were normalized by lipid infusion. In isolated adipocytes, visfatin was released into supernatant medium by acute addition and long-term treatment of rosiglitazone. This secretion was blocked by synthetic fatty acids and by inhibition of phosphatidylinositol 3-kinase or Akt. In conclusion, release of the insulin-mimetic visfatin may represent a major mechanism of metabolic TZD action. The presence of FFA antagonizes this action, which may have implications for visfatin bioactivity.
噻唑烷二酮类药物（TZDs）可改善2型糖尿病患者游离脂肪酸（FFAs）升高对胰岛素敏感性产生的有害影响。目前尚不清楚TZDs的这种有益作用是否与胰岛素模拟脂肪细胞因子内脂素释放的改变有关。在本研究中，我们调查了内脂素浓度是否会因FFA和TZDs治疗而改变。在一项随机、双盲、安慰剂对照、平行组研究中，16名健康志愿者在接受罗格列酮（8毫克/天，n = 8）或安慰剂（n = 8）治疗3周后，接受甘油三酯/肝素输注以增加血浆FFA，并测量循环血浆内脂素。作为推论，将人脂肪细胞与合成脂肪酸和罗格列酮一起孵育，以评估体外内脂素的释放。结果显示，罗格列酮治疗使全身血浆内脂素浓度从0.6±0.1升高至1.7±0.2纳克/毫升（P < 0.01）。脂质输注导致血浆FFA显著升高，但对对照组的循环内脂素无影响。相比之下，接受罗格列酮治疗的受试者中升高的内脂素浓度通过脂质输注恢复正常。在分离的脂肪细胞中，急性添加和长期使用罗格列酮治疗可使内脂素释放到上清培养基中。这种分泌被合成脂肪酸以及磷脂酰肌醇3激酶或Akt的抑制所阻断。总之，胰岛素模拟内脂素的释放可能代表了TZDs代谢作用的主要机制。FFA的存在拮抗了这种作用，这可能对内脂素的生物活性有影响。
