Development of insulin resistance and endothelin-1 levels in the Zucker fatty rat

被引:13
|
作者
Berthiaume, N [1 ]
Mika, AK [1 ]
Zinker, BA [1 ]
机构
[1] Abbott Labs, Dept R47M, Global Pharmaceut Res & Dev Div, Abbott Pk, IL 60064 USA
来源
METABOLISM-CLINICAL AND EXPERIMENTAL | 2003年 / 52卷 / 07期
关键词
D O I
10.1016/S0026-0495(03)00098-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2003 Elsevier Inc. All rights reserved.
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页码:845 / 849
页数:5
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