Gong Y, Li J, Li C, Mu Y, Xiao Y, Tian H, Pan C, Liu Y
Department of Endocrinology, The Chinese People's Liberation Army General Hospital, Beijing, China.
J Int Med Res. 2012;40(4):1304-16. doi: 10.1177/147323001204000409.
To explore the adipose tissue endocrine mechanism of pioglitazone and its possible prophylactic role in insulin resistance.
Male Wistar rats were randomized to receive a normal diet (N group), a high-fat insulin resistance-inducing diet (IR group), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken. HepG2 cells were cultured with palmitic acid (PA), pioglitazone and PA plus pioglitazone, and RNA interference was used to downregulate adiponectin receptor (AdipoR) 2 in these cells. The mRNA and protein levels of adipokines (resistin and adiponectin), AdipoR1 and 2 and uptake of [3H]-labelled glucose were measured in the HepG2 cells.
Resistin and adiponectin in adipose tissue and AdipoR2 in liver tissue were significantly decreased in the IR group compared with the N group. Adiponectin and AdipoR2 were significantly increased and insulin resistance significantly decreased in the P group versus the IR group. In HepG2 cells, AdipoR2 levels and glucose uptake decreased significantly when PA was ≥200 μM, but were elevated by pioglitazone. Small interfering RNA-AdipoR2 confirmed glucose uptake in liver was regulated by AdipoR2.
Pioglitazone prevented insulin resistance in rats fed a high-fat diet. Liver AdipoR2-mediated glucose uptake is important in the prophylactic effect of pioglitazone on insulin resistance.
探讨吡格列酮的脂肪组织内分泌机制及其对胰岛素抵抗可能的预防作用。
将雄性Wistar大鼠随机分为正常饮食组（N组）、高脂诱导胰岛素抵抗饮食组（IR组）或高脂饮食加吡格列酮治疗组（P组）。在开始饮食后的第10周和第11周检测葡萄糖耐量和胰岛素抵抗，并在第12周采集脂肪、肝脏和骨骼肌组织样本。用棕榈酸（PA）、吡格列酮以及PA加吡格列酮培养HepG2细胞，并利用RNA干扰下调这些细胞中的脂联素受体（AdipoR）2。检测HepG2细胞中脂肪因子（抵抗素和脂联素）、AdipoR1和2的mRNA和蛋白水平以及[3H]标记葡萄糖的摄取。
与N组相比，IR组脂肪组织中的抵抗素和脂联素以及肝脏组织中的AdipoR2显著降低。与IR组相比，P组脂联素和AdipoR2显著升高，胰岛素抵抗显著降低。在HepG2细胞中，当PA≥200μM时，AdipoR2水平和葡萄糖摄取显著降低，但吡格列酮可使其升高。小干扰RNA-AdipoR2证实肝脏中的葡萄糖摄取受AdipoR2调节。
吡格列酮可预防高脂饮食喂养大鼠的胰岛素抵抗。肝脏AdipoR2介导的葡萄糖摄取在吡格列酮对胰岛素抵抗的预防作用中起重要作用。
