Dhindsa Sandeep, Tripathy Devjit, Sanalkumar Nishanth, Ravishankar Shreyas, Ghanim Husam, Aljada Ahmad, Dandona Paresh
Diabetes-Endocrinology Center of Western New York, Distinguished Chief of Endocrinology, State University of New York at Buffalo, 3 Gates Circle, Buffalo, New York 14209, USA.
J Clin Endocrinol Metab. 2005 Sep;90(9):5058-63. doi: 10.1210/jc.2005-0223. Epub 2005 Jun 28.
Elevation of free fatty acids (FFAs) by the infusion of triglyceride-heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR.
Nine obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were performed during 0-2 and 4-6 h of TG-Hep.
After rosiglitazone for 6 wk, fasting FFA concentration fell, but not significantly (489 +/- 63 at 0 wk; 397 +/- 58 micromol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 +/- 0.95 at 0 wk; 2.03 +/- 0.45 microg/ml at 6 wk) and serum amyloid A (17.36 +/- 4.63 at 0 wk; 8.77 +/- 1.63 microg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 +/- 0.95 mg/kg.min to 3.02 +/- 0.59 mg/kg.min (P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 +/- 0.81 mg/kg.min (P = 0.03 vs. 0 wk), which decreased to 4.52 +/- 0.53 mg/kg.min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in GIR induced by TG-Hep infusion was similar before and after rosiglitazone therapy [1.47 +/- 0.50 vs. 1.77 0.3 mg/kg.min (28.9 +/- 6.5 vs. 26.4 +/- 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for triglycerides).
We conclude that rosiglitazone: 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, C-reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.
通过输注甘油三酯-肝素乳剂（TG-Hep）使游离脂肪酸（FFA）升高会导致胰岛素抵抗（IR）。我们研究了胰岛素增敏剂（罗格列酮）对FFA诱导的IR的影响。
9名肥胖受试者在接受罗格列酮（8毫克/天）治疗6周前后，分别进行了6小时的TG-Hep输注。在TG-Hep输注的0至2小时和4至6小时期间进行了高胰岛素-正常血糖钳夹试验。
罗格列酮治疗6周后，空腹FFA浓度下降，但不显著（0周时为489±63；6周时为397±58微摩尔/升；P = 0.16），而C反应蛋白（0周时为4.26±0.95；6周时为2.03±0.45微克/毫升）和血清淀粉样蛋白A（0周时为17.36±4.63；6周时为8.77±1.63微克/毫升）显著下降。在0周时，TG-Hep输注导致葡萄糖输注率（GIR）从4.49±0.95毫克/千克·分钟降至3.02±0.59毫克/千克·分钟（P = 0.018）。罗格列酮治疗使基线GIR增加至6.29±0.81毫克/千克·分钟（与0周相比，P = 0.03），在TG-Hep输注6小时后降至4.52±0.53毫克/千克·分钟（P = 0.001）。罗格列酮治疗前后，TG-Hep输注引起的GIR下降相似[1.47±0.50对1.77±0.3毫克/千克·分钟（28.9±6.5对26.4±3.7%）；P = 0.51]。TG-Hep输注后FFA和甘油三酯的升高在6周时显著降低（FFA的P = 作者可能有误，这里应该是0.006；甘油三酯的P = 0.024）。
我们得出结论，罗格列酮：1）使GIR显著增加；2）导致炎症介质、C反应蛋白和血清淀粉样蛋白A减少；3）降低TG-Hep输注后FFA和甘油三酯的升高；4）不能预防FFA诱导的IR。
