Blaak E E, Wagenmakers A J, Glatz J F, Wolffenbuttel B H, Kemerink G J, Langenberg C J, Heidendal G A, Saris W H
Department of Human Biology, Maastricht University and Academic Hospital, 6200 MD Maastricht, The Netherlands.
Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E146-54. doi: 10.1152/ajpendo.2000.279.1.E146.
In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129 vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.
在本研究中,我们探讨了以下假设:2型糖尿病患者在过夜禁食状态和β-肾上腺素能刺激期间,前臂骨骼肌游离脂肪酸(FFA)代谢存在受损情况。对8名肥胖的2型糖尿病患者和8名非肥胖对照者(Con)进行了研究,在过夜禁食后以及输注非选择性β-激动剂异丙肾上腺素(Iso,20 ng·kg去脂体重⁻¹·min⁻¹)期间,采用前臂平衡技术和间接测热法,并输注稳定同位素示踪剂[U-(¹³)C]棕榈酸。此外,还测定了股外侧肌活检组织中线粒体酶和细胞质脂肪酸结合蛋白(FABP)的活性。在禁食和输注Iso期间,示踪剂平衡数据均显示,与Con相比,2型糖尿病患者前臂肌肉FFA摄取量较低(Con与2型糖尿病:禁食时为449±69 vs. 258±42,输注Iso时为715±129 vs. 398±70 nmol·100 ml组织⁻¹·min⁻¹,P<0.05),FFA释放量也较低。而且,在输注Iso期间,2型糖尿病患者骨骼肌对血浆FFA的氧化减弱(Con与2型糖尿病:输注Iso时为446±274 vs. 16±70 nmol·100 ml组织⁻¹·min⁻¹,P<0.05)。2型糖尿病患者前臂甘油净释放量增加(P<0.05),这表明前臂脂肪分解增加。此外,2型糖尿病患者骨骼肌细胞质FABP含量和肌肉氧化酶活性降低。我们得出结论,无论有无Iso刺激,2型糖尿病患者在过夜禁食状态下,其前臂肌肉对血浆FFA的摄取和氧化均受损。