Berthiaume Nathalie, Mika Amanda K, Zinker Bradley A
Global Pharmaceutical Research, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Metabolism. 2003 Jul;52(7):845-9. doi: 10.1016/s0026-0495(03)00098-2.
In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and fatty rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The fatty rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in fatty versus lean rats (3.2+/-0.5 v 2.0+/-0.3 pg/mL, respectively; P<.05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between fatty and lean rats were not different during the MTT (15 minutes: 2.9+/-0.4 v 2.7+/-0.7; 120 minutes: 6.5+/-0.8 v 6.6+/-0.5 pg/mL, fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, fatty rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9+/-1.4 v 1.8+/-0.4; 120 minutes: 9.4+/-1.7 v 3.2+/-0.5 pg/mL, respectively; P<.01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in fatty versus lean rats 15 minutes following the challenge (3.4+/-0.4 v 2.4+/-0.2 pg/mL, respectively; P<.05). In conclusion, ET-1 levels in the Zucker fatty rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.
为了确定胰岛素抵抗增加对内皮素 -1（ET-1）水平的影响，对7周、12周和15周龄的Zucker瘦型和肥胖型大鼠进行了基础状态下以及完整营养餐耐量试验（MTT）期间的研究。与瘦型动物相比，肥胖型大鼠在所有年龄段均有轻度高血糖、严重高胰岛素血症和葡萄糖不耐受，且如先前发表的那样，在各年龄组内随年龄增长而加重。7周龄时，肥胖型大鼠的基础ET-1水平显著高于瘦型大鼠（分别为3.2±0.5 vs 2.0±0.3 pg/mL；P<0.05）；然而，在12周或15周时，我们未观察到任何显著的基础差异。7周龄时，在MTT期间肥胖型和瘦型大鼠的ET-1水平无差异（15分钟时：2.9±0.4 vs 2.7±0.7；120分钟时：6.5±0.8 vs 6.6±0.5 pg/mL，分别为肥胖型和瘦型）。12周龄时，尽管基础水平无差异，但与瘦型动物相比，肥胖型大鼠在MTT期间的ET-1水平更高（15分钟时：6.9±1.4 vs 1.8±0.4；120分钟时：9.4±1.7 vs 3.2±0.5 pg/mL，分别为肥胖型和瘦型；P<0.01）。15周龄时，MTT期间的ET-1水平降至与7周龄时观察到的水平相似，在挑战后15分钟时，肥胖型大鼠的ET-1水平显著高于瘦型大鼠（分别为3.4±0.4 vs 2.4±0.2 pg/mL；P<0.05）。总之，Zucker肥胖型大鼠的ET-1水平：（1）在7周龄胰岛素抵抗进展的早期阶段升高，但此后在基础条件下随年龄增长无变化；（2）在胰岛素抵抗进展至12周的营养挑战条件下升高，且在15周龄时仍显著升高，但升高程度较小。这些结果的解释及其与观察到的胰岛素抵抗的关系尚不清楚，并需要进一步研究。
