Fink R I, Huecksteadt T, Karaoghlanian Z
Endocrinology. 1986 Mar;118(3):1139-47. doi: 10.1210/endo-118-3-1139.
We have studied glucose metabolism in adipocytes from younger (6 months) and older (24 months) Fischer rats. Insulin binding was similar in both groups, expressed per cell number (2.67 +/- 0.41% vs. 2.96 +/- 0.38%) or per cell surface area (4.59 +/- 0.70% vs. 4.15 +/- 0.53%) in the 6- and 24-month-old animals, respectively. Maximal insulin-stimulated 3-O-methylglucose transport was decreased by 40% in the older group (0.234 +/- 0.032) compared with that in the younger group (0.411 +/- 0.031 pmol/2 X 10(9) micron 2 X sec (P less than 0.01), with no change in basal rates of transport. The decrease in glucose transport was due to a 36% reduction in the maximum velocity (91 pmol/sec in the younger vs. 59 pmol/sec in the older group), with no change in the Km. Postglucose transport steps of glucose metabolism, including CO2 oxidation, triglyceride synthesis, and lactate production, were measured at a higher glucose concentration (2 mM), where glucose transport is not rate limiting. Overall maximal insulin-stimulated glucose metabolism was decreased by 45% in the older group (15.6 nmol) compared with that in the younger group (28.6 nmol/10(5) cells X h; P less than 0.05). Glucose oxidation was decreased by 42% (2.9 vs. 5.0 nmol/10(5) cells X h; P less than 0.05), triglyceride synthesis by 40% (5.9 vs. 9.8 nmol/10(5) cells X h; P less than 0.05), and lactate production by 47% (6.3 vs. 11.8 nmol/10(5) cells X h; P less than 0.05). We conclude that in adipocytes from aged Fischer rats, cellular insulin resistance is due to multiple post-binding defects involving the glucose transport system and more distal intracellular processes.
我们研究了年轻（6个月）和老年（24个月）的费希尔大鼠脂肪细胞中的葡萄糖代谢。两组细胞的胰岛素结合情况相似，按细胞数量计算（6个月龄和24个月龄动物分别为2.67±0.41%对2.96±0.38%），或按细胞表面积计算（分别为4.59±0.70%对4.15±0.53%）。与年轻组（0.411±0.031 pmol/2×10⁹μm²×秒）相比，老年组最大胰岛素刺激的3 - O - 甲基葡萄糖转运降低了40%（0.234±0.032）（P<0.01），基础转运速率无变化。葡萄糖转运的降低是由于最大速度降低了36%（年轻组为91 pmol/秒，老年组为59 pmol/秒），而米氏常数（Km）不变。在较高葡萄糖浓度（2 mM）下测量了葡萄糖代谢中葡萄糖转运后的步骤，包括二氧化碳氧化、甘油三酯合成和乳酸生成，此时葡萄糖转运不是限速步骤。与年轻组（28.6 nmol/10⁵细胞×小时）相比，老年组总体最大胰岛素刺激的葡萄糖代谢降低了45%（15.6 nmol）（P<0.05）。葡萄糖氧化降低了42%（2.9对5.0 nmol/10⁵细胞×小时；P<0.05），甘油三酯合成降低了40%（5.9对9.8 nmol/10⁵细胞×小时；P<0.05），乳酸生成降低了47%（6.3对11.8 nmol/10⁵细胞×小时；P<0.05）。我们得出结论，在老年费希尔大鼠的脂肪细胞中，细胞胰岛素抵抗是由于涉及葡萄糖转运系统和更远端细胞内过程的多个结合后缺陷所致。
