Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, Missouri 63110, USA.
J Clin Endocrinol Metab. 2012 Jul;97(7):E1219-23. doi: 10.1210/jc.2012-1035. Epub 2012 Apr 6.
Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity.
The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects.
We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods.
Basal (r(s) = -0.379, P < 0.001) and insulin-suppressed (r(s) = -0.631, P < 0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P < 0.001).
These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.
增加脂肪组织的脂肪分解活性被认为是肥胖相关骨骼肌胰岛素抵抗发病机制中的一个重要因素。
本研究旨在评估人体游离脂肪酸（FFA）向血浆中释放率与骨骼肌胰岛素敏感性之间的关系。
我们通过使用稳定同位素示踪法，在 110 名非糖尿病女性（体重指数 20.6-46.4kg/m2）中，测定了基础状态和胰岛素输注期间（模拟餐后胰岛素浓度）每公斤去脂体重的棕榈酸出现率（FFA 向瘦组织供应的指标）和骨骼肌胰岛素敏感性，后者定义为葡萄糖清除率的百分比增加。通过高胰岛素-正常血糖钳夹程序。
基础状态（r(s) = -0.379，P < 0.001）和胰岛素抑制状态（r(s) = -0.631，P < 0.001）的棕榈酸出现率与骨骼肌胰岛素敏感性呈负相关。然而，当脂肪分解率和 FFA 利用率降低到基础值的 20%以下时，胰岛素输注期间的棕榈酸出现率与基础状态下的棕榈酸出现率相比，其相关性更强（P = 0.0007）。棕榈酸出现率的相对抑制与胰岛素输注期间葡萄糖清除率的相对刺激呈直接相关（r(s) = 0.530，P < 0.001）。
这些数据表明，FFA 动力学与肌肉葡萄糖代谢之间的相关性是由于多器官胰岛素抵抗，而不是 FFA 本身对骨骼肌胰岛素作用的直接影响，这挑战了增加脂肪组织脂肪分解率是胰岛素抵抗的一个重要原因的观点。
