OBESITY AND INSULIN RESISTANCE - LESSONS LEARNED FROM THE PIMA-INDIANS
OBESITY AND INSULIN RESISTANCE - LESSONS LEARNED FROM THE PIMA-INDIANS
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DOI：
10.1002/dmr.5610040508
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发表时间：
1988-08-01
期刊：
影响因子：
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通讯作者：
BOGARDUS, C
中科院分区：
文献类型：
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作者：
LILLIOJA, S;BOGARDUS, C
糖尿病和肥胖症在美国西南部的皮马印第安人中流行，并且糖尿病的患病率正在增加。肥胖和糖尿病之间最可能的联系是组织胰岛素抵抗。如果肥胖被定义为身体脂肪过多，那么它只能通过测量身体成分来准确评估，而不是通过身体质量指数或理想体重百分比等近似值。为了比较不同大小的个体的代谢数据，需要代谢大小的准确测量。总体重不是比较个体的适当方法，因为肥胖受试者的非代谢质量（甘油三酯）比例更大。体表面积显示出性别差异，如果两性都存在，这可能会扭曲数据。从代谢率的研究中，我们已经确定，代谢率是间接成正比的无脂肪的质量加上18公斤，我们建议，这个重量可以等同于代谢大小。葡萄糖在骨骼肌中的储存似乎在静脉内葡萄糖负荷的处置中是重要的。与其在糖原储存中的作用一致，糖原合成酶在高胰岛素、正常血糖钳夹期间与处置葡萄糖的能力成比例地被激活。糖原合酶的作用是最显着的超生理血浆胰岛素浓度，因为在这些胰岛素浓度的葡萄糖摄取是高度家族独立的肥胖程度，我们认为，可能有一个特定的基因缺陷表达在骨骼肌，降低胰岛素的反应性在一些科目。在代谢室中测量的24小时呼吸商（脂肪来源的卡路里的比例的测量）与肥胖程度之间缺乏相关性表明，在肥胖的皮马印第安人中，胰岛素抵抗不是由于游离脂肪酸（葡萄糖-脂肪酸-酮循环）抑制葡萄糖代谢。与瘦状态相比，肥胖与无脂肪质量增加几乎千克-对于有脂肪质量的千克。这种无脂肪组织的增加在产生胰岛素抵抗中的作用在过去没有得到足够的重视。随着无脂肪质量的增加，肌肉细胞肥大，肌肉中的毛细血管间隔更宽。我们认为，这些生物物理变化在肌肉介导，至少部分，肥胖症的影响，产生胰岛素敏感性降低和胰岛素作用的异常动力学在肥胖症。因此，我们认为胰岛素抵抗是遗传缺陷和肥胖引起的骨骼肌生物物理特性变化的结合。这些缺陷可能反过来导致非胰岛素依赖型糖尿病的发展。
Diabetes and obesity are epidemic in the Pima Indians of the Southwestern United States, and the prevalence of diabetes is increasing. The most likely link between obesity and diabetes is tissue insulin resistance. If obesity is defined as an excess of body fat, then it can only be accurately assessed by measurements of body composition and not by approximations such as body mass index or percent of ideal weight. To compare the metabolic data of individuals of varying size, an accurate measure of metabolic size is needed. Total body weight is not an appropriate means of comparing individuals since obese subjects have a greater proportion of nonmetabolizing mass (triglyceride). Body surface area shows a sex difference, and this may distort data if both sexes are present. From studies of metabolic rate we have determined that metabolic rate is indirectly proportional to the fat-free mass plus 18 kg, and we suggest that this weight can be equated with metabolic size. Glucose storage in skeletal muscle appears to be important in the disposal of an intravenous glucose load. Consistent with its role in glycogen storage, glycogen synthase enzyme is activated in proportion to the ability to dispose of glucose during a hyperinsulinemic, euglycemic clamp. The role of glycogen synthase is most notable at supraphysiological plasma insulin concentrations; and since glucose uptake at these insulin concentrations is highly familial independent of the degree of obesity, we suggest that there may be a specific genetic defect expressed in skeletal muscle that reduces insulin responsiveness in some subjects. The lack of correlation between 24 hour respiratory quotient measured in a metabolic chamber (a measure of the proportion of fat derived calories) and degree of obesity indicates that in obese Pima Indians insulin resistance is not due to an inhibition of glucose metabolism by free fatty acids (glucose-fatty acid-ketone cycle). Obesity is associated with an increase in fat-free mass almost kilogram- for kilogram with fat mass when compared to the lean state. A role for this increase in fat-free tissue in producing insulin resistance has been given insufficient attention in the past. With an increase in fat-free mass, muscle cells are hypertrophied and capillaries in muscle are more widely spaced. We propose that these biophysical changes in muscle mediate, at least in part, the effects of obesity to produce a reduction in insulin sensitivity and the abnormal kinetics of insulin action found in the obese. We suggest therefore that insulin resistance is a combination of a genetic defect and obesity-induced changes in the biophysical properties of skeletal muscle. These defects may in turn lead to the development of non-insulin-dependent diabetes mellitus.