Hammarstedt A, Pihlajamäki J, Graham T E, Kainulainen S, Kahn B B, Laakso M, Smith U
The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
J Intern Med. 2008 Apr;263(4):440-9. doi: 10.1111/j.1365-2796.2007.01914.x.
High levels of circulating retinol-binding protein 4 (RBP4) and baseline expression of adipogenic genes correlate with subsequent improvement in insulin sensitivity following Thiazolidinedione (TZD) treatment.
The aim was to identify baseline characteristics and early changes related to TZD treatment that could predict a good treatment response.
Subjects were examined with oral glucose tolerance test, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, body composition and standard blood sampling at baseline and after 4 and 12 weeks treatment. Subcutaneous adipose tissue biopsies were taken from the abdominal region at baseline, after 3 days and 4 weeks treatment to examine the gene expression profile.
Research laboratory in a University hospital.
Ten newly diagnosed and previously untreated type 2 diabetic subjects were treated with pioglitazone for 3 months.
Baseline characteristics and early changes related to TZD treatment that could predict the response after 3 months.
Pioglitazone improved insulin sensitivity after 4 weeks combined with lower glucose and insulin levels without any change in BMI. It was accompanied by lower circulating resistin and plasminogen activator inhibitor-1 levels rapidly increased levels of circulating total and high molecular weight adiponectin as well as adiponectin and adipocyte fatty acid-binding protein (aP2) mRNA expression in the adipose tissue. High levels of circulating RBP4 at baseline and adipose tissue expression of aP2, proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and uncoupling protein 2 (UCP-2) predicted a good treatment response measured as improvement in insulin-stimulated whole-body glucose uptake after 3 months.
Circulating levels of RBP4 as an index of insulin sensitivity and mRNA levels of adipogenic genes correlate with the subsequent improvement in insulin sensitivity following TZD treatment.
循环视黄醇结合蛋白4（RBP4）的高水平以及脂肪生成基因的基线表达与噻唑烷二酮（TZD）治疗后胰岛素敏感性的后续改善相关。
旨在确定与TZD治疗相关的基线特征和早期变化，这些特征和变化可预测良好的治疗反应。
在基线以及治疗4周和12周后，对受试者进行口服葡萄糖耐量试验、静脉葡萄糖耐量试验、高胰岛素正常血糖钳夹试验、身体成分分析和标准血液采样。在基线、治疗3天和4周后，从腹部区域采集皮下脂肪组织活检样本，以检查基因表达谱。
大学医院的研究实验室。
10名新诊断且未经治疗的2型糖尿病受试者接受了吡格列酮治疗3个月。
与TZD治疗相关的基线特征和早期变化，这些变化可预测3个月后的反应。
吡格列酮在4周后改善了胰岛素敏感性，同时降低了血糖和胰岛素水平，而体重指数（BMI）无任何变化。这伴随着循环抵抗素和纤溶酶原激活物抑制剂-1水平降低，循环总脂联素和高分子量脂联素水平迅速升高，以及脂肪组织中脂联素和脂肪细胞脂肪酸结合蛋白（aP2）mRNA表达增加。基线时循环RBP4的高水平以及脂肪组织中aP2、增殖激活受体γ辅激活因子1α（PGC-1α）和解偶联蛋白2（UCP-2）的表达预测了良好的治疗反应，以3个月后胰岛素刺激的全身葡萄糖摄取改善来衡量。
作为胰岛素敏感性指标的循环RBP4水平以及脂肪生成基因的mRNA水平与TZD治疗后胰岛素敏感性的后续改善相关。
