van Loon L J C, Manders R J F, Koopman R, Kaastra B, Stegen J H C H, Gijsen A P, Saris W H M, Keizer H A
Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Diabetologia. 2005 Oct;48(10):2097-107. doi: 10.1007/s00125-005-1889-x. Epub 2005 Aug 12.
AIMS/HYPOTHESIS: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients.
We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type.
Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05).
CONCLUSIONS/INTERPRETATION: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.
目的/假设：在本研究中，我们调查了脂肪组织脂解抑制对2型糖尿病患者骨骼肌底物利用的影响。
我们研究了10名2型糖尿病患者在以下条件下的情况：(1) 静息时；(2) 在最大工作量能力的50%进行60分钟的骑行运动及随后的恢复过程中。研究在正常禁食条件下（对照试验：CON）以及给予烟酸类似物后（低血浆非酯化脂肪酸试验：LFA）进行。持续输注[U-13C]棕榈酸酯和[6,6 -2H2]葡萄糖，以量化血浆非酯化脂肪酸（NEFA）和葡萄糖氧化率，并估计肌肉内三酰甘油（IMTG）和糖原的利用情况。在运动前后采集肌肉活检样本，以确定特定肌纤维类型的脂质和糖原含量的净变化。
给予烟酸类似物（阿昔莫司）后，血浆NEFA的出现率有效降低，导致LFA试验中的NEFA浓度较低（p<0.001）。在LFA试验中，静息时、运动期间及随后的恢复过程中，血浆NEFA氧化率大幅降低。较低的血浆NEFA氧化率通过IMTG和内源性碳水化合物利用的增加得到补偿（p<0.05）。各试验之间的血浆葡萄糖处置率无差异。与示踪数据一致，在LFA试验中运动后观察到I型肌纤维脂质含量有更大的净下降（p<0.05）。
结论/解读：本研究表明血浆NEFA的可用性调节IMTG的利用，并且脂肪组织脂解抑制与运动相结合，可能是在过夜禁食状态下增加2型糖尿病患者肌肉内脂质和糖原利用的有效手段。
