Effect of age and moderate food restriction on insulin sensitivity in Wistar rats:: role of adiposity
Effect of age and moderate food restriction on insulin sensitivity in Wistar rats:: role of adiposity
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DOI：
10.1677/joe.1.07043
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Carrascosa, Jose M.
中科院分区：
文献类型：
--
作者：
Escriva, Fernando;Gavete, M. Lucia;Carrascosa, Jose M.
胰岛素抵抗在人类和啮齿动物中随着年龄的增长而发展。在此，我们研究了胰岛素敏感性随年龄的变化，试图区分肥胖在这一过程中的作用。我们对3、8、24月龄大鼠进行了口服葡萄糖耐量试验，并测定了自由喂养的3、8、24月龄大鼠以及热量限制3个月后的8、24月龄大鼠在正糖-高胰岛素条件下的总体和组织特异性葡萄糖利用情况。分析了机体成分和脂肪细胞来源的细胞因子，如瘦素、抵抗素和脂联素。总体而言，胰岛素敏感性随着年龄的增长而下降。限制卡路里可以改善8个月大的大鼠的整体胰岛素敏感性，但对24个月大的大鼠没有效果。胰岛素刺激的葡萄糖在脂肪组织中的利用在8个月后下降，而在氧化肌肉中，只有在老年大鼠中才有意义。热量限制仅在8个月大的大鼠中恢复脂肪组织胰岛素敏感性，而在24个月大的大鼠肌肉中没有观察到变化。抵抗素和瘦素随着年龄的增长而增加。在8个月大的老鼠中，食物限制会降低抵抗素，增加脂联素，并降低两个年龄段的瘦素。内脏脂肪和总脂肪随着年龄的增长而增加，在卡路里限制后减少。我们得出结论，内脏脂肪的增加在性成熟后胰岛素抵抗的发展中起关键作用；这是可以通过限制卡路里来逆转的。随着年龄的增长，腹膜后脂肪和全身脂肪的积累导致肌肉葡萄糖摄取受损，并导致难以逆转的胰岛素抵抗状态。
Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity front that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyper-insulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8- and 24-month-old rats after 3 months of caloric restriction. Body composition and adipocyte-derived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8- but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity; which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.