DEVELOPMENT OF MUSCLE INSULIN RESISTANCE AFTER LIVER INSULIN RESISTANCE IN HIGH-FAT FED RATS
DEVELOPMENT OF MUSCLE INSULIN RESISTANCE AFTER LIVER INSULIN RESISTANCE IN HIGH-FAT FED RATS
复制标题
DOI：
10.2337/diabetes.40.11.1397
复制
发表时间：
1991-11-01
期刊：
影响因子：
7.7
通讯作者：
STORLIEN, LH
中科院分区：
文献类型：
--
作者：
KRAEGEN, EW;CLARK, PW;STORLIEN, LH
肌肉和肝脏胰岛素抵抗是非胰岛素依赖型糖尿病的两个主要缺陷。饮食因素可能是胰岛素抵抗的重要病因。我们研究了成年雄性Wistar大鼠组织中高脂饮食诱导的胰岛素抵抗的进展性变化。在体内胰岛素的作用进行了比较3天和3周后，等热量的合成高脂肪或高淀粉饲料（59和10%卡作为脂肪，分别）。在清醒的5- 7小时禁食状态下，使用正葡萄糖钳夹（600 pM胰岛素）和[3-H-3]-葡萄糖输注评估基础和胰岛素刺激的葡萄糖代谢。脂肪喂养可显著降低胰岛素对肝脏葡萄糖输出的抑制作用（P < 0.01）。然而，胰岛素介导的外周葡萄糖处置的显着损害仅存在3周的饮食后。进一步的体内[H-3]-2-脱氧葡萄糖摄取研究支持了这一发现，并证明了高脂喂养3天后脂肪而非肌肉胰岛素抵抗。与淀粉喂养对照组相比，脂肪喂养引起的肌肉甘油三酯积累在第3天并不显著，但在第3周时红色肌肉中增加了一倍（P < 0.001）。到3周时，高脂肪喂养的动物已出现明显的葡萄糖耐受不良。我们的结论是，脂肪喂养诱导胰岛素抵抗的肝脏和脂肪组织之前，骨骼肌与早期代谢变化，有利于过度供应的能量底物骨骼肌相对于代谢的需要。这可能会产生后来的肌肉胰岛素抵抗。
Muscle and hepatic insulin resistance are two major defects of non-insulin-dependent diabetes mellitus. Dietary factors may be important in the etiology of insulin resistance. We studied progressive changes in the development of high-fat-diet-induced insulin resistance in tissues of the adult male Wistar rat. In vivo insulin action was compared 3 days and 3 wk after isocaloric synthetic high-fat or high-starch feeding (59 and 10% cal as fat, respectively). Basal and insulin-stimulated glucose metabolism were assessed in the conscious 5- to 7-h fasted state with the euglycemic clamp (600 pM insulin) with a [3-H-3]-glucose infusion. Fat feeding significantly reduced suppressibility of hepatic glucose output by insulin after both 3 days and 3 wk of diet (P < 0.01). However, a significant impairment of insulin-mediated peripheral glucose disposal was only present after 3 wk of diet. Further in vivo [H-3]-2-deoxyglucose uptake studies supported this finding and demonstrated adipose but not muscle insulin resistance after 3 days of high-fat feeding. Muscle triglyceride accumulation due to fat feeding was not significant at 3 days but had doubled by 3 wk in red muscle (P < 0.001) compared with starch-fed controls. By 3 wk, high-fat-fed animals had developed significant glucose intolerance. We conclude that fat feeding induces insulin resistance in liver and adipose tissue before skeletal muscle with early metabolic changes favoring an oversupply of energy substrate to skeletal muscle relative to metabolic needs. This may generate later muscle insulin resistance.