Ye Ji-Ming, Dzamko Nick, Hoy Andrew J, Iglesias Miguel A, Kemp Bruce, Kraegen Edward
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia.
Diabetes. 2006 Oct;55(10):2797-804. doi: 10.2337/db05-1315.
AMP-activated protein kinase (AMPK) has been implicated in the insulin-sensitizing actions of thiazolidinediones (TZDs), but it is not known whether TZD treatment can enhance tissue glucose uptake in response to AMPK activation. The present study investigated the influence of the TZD rosiglitazone on glucose turnover induced by intravenous infusion of the AMPK activator 5-aminoimidazole 4-carboxamide riboside (AICAR) under euglycemic and iso-insulinemic conditions in insulin-resistant high-fat-fed rats. We found that rosiglitazone treatment significantly enhanced AICAR-stimulated whole-body glucose disposal by 27% in high-fat-fed rats, and a 44% greater glucose infusion rate (both P < 0.01 vs. vehicle control rats) was required to maintain euglycemia. Along with this, both AICAR-stimulated glucose uptake and glucose incorporation into glycogen in muscle and adipose tissue were enhanced (P < 0.05). The enhanced glucose uptake and glycogen synthesis in muscle were associated with increased activity of total AMPK and the AMPKalpha2 subunit. In comparison, these effects were not apparent in rats fed standard rodent diet. Thus, our findings suggest that in addition to ameliorating insulin resistance, TZDs may enhance AMPK-stimulated glucose clearance into peripheral tissues in insulin-resistant states.
AMP激活的蛋白激酶（AMPK）与噻唑烷二酮类药物（TZDs）的胰岛素增敏作用有关，但尚不清楚TZDs治疗是否能通过激活AMPK来增强组织对葡萄糖的摄取。本研究调查了在正常血糖和等胰岛素条件下，TZDs罗格列酮对胰岛素抵抗的高脂喂养大鼠静脉输注AMPK激活剂5-氨基咪唑-4-甲酰胺核苷（AICAR）诱导的葡萄糖代谢的影响。我们发现，罗格列酮治疗显著增强了高脂喂养大鼠中AICAR刺激的全身葡萄糖处置，提高了27%，并且需要更高44%的葡萄糖输注速率（与溶剂对照大鼠相比，两者P < 0.01）来维持正常血糖。与此同时，AICAR刺激的肌肉和脂肪组织中葡萄糖摄取及葡萄糖合成糖原均增强（P < 0.05）。肌肉中葡萄糖摄取和糖原合成的增强与总AMPK及AMPKα2亚基活性增加有关。相比之下，这些作用在标准啮齿动物饮食喂养的大鼠中并不明显。因此，我们的研究结果表明，除了改善胰岛素抵抗外，TZDs可能还会增强胰岛素抵抗状态下AMPK刺激的外周组织对葡萄糖的清除。
