Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients
Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients
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DOI：
10.1210/jc.2008-1400
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发表时间：
2009-03-01
影响因子：
5.8
通讯作者：
Jordan, Jens
中科院分区：
文献类型：
--
作者：
Boschmann, Michael;Engeli, Stefan;Jordan, Jens
背景：二肽基肽酶- iv （DPP-4）抑制可增加内源性GLP-1活性，从而改善2型糖尿病患者的血糖控制。代谢反应可以部分解释为胰腺外机制。目的：我们验证了维格列汀抑制DPP-4引起脂肪组织和骨骼肌代谢变化的假设。设计与环境：我们在一个学术临床研究中心进行了一项随机、双盲、交叉研究。患者：20例2型糖尿病患者，体重指数28 ~ 40 kg/m(2)。干预：干预包括使用选择性DPP-4抑制剂维格列汀或安慰剂治疗7天，并在第7天进行标准化试验餐。主要观察指标：测定静脉DPP-4活性、儿茶酚胺、游离脂肪酸、甘油、葡萄糖、（原）胰岛素、透析液葡萄糖、乳酸、丙酮酸、甘油。结果：空腹和餐后静脉胰岛素、葡萄糖、甘油、甘油三酯和游离脂肪酸浓度与维格列汀组和安慰剂组没有差异。维格列汀增强餐后血浆去甲肾上腺素的升高。此外，维格列汀增加脂肪组织中透析液甘油和乳酸浓度，同时抑制骨骼肌中透析液乳酸和丙酮酸浓度。呼吸商随膳食摄入而增加，但维格列汀持续降低。结论：我们的研究首次表明DPP-4抑制增加餐后脂质动员和氧化。这种反应可以解释为交感神经的激活，而不是对代谢状态的直接影响。[J] .中华内分泌杂志，2009:846-852。
Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extrapancreatic mechanisms.Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism.Design and Setting: We conducted a randomized, double-blind, crossover study at an academic clinical research center.Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2), participated.Intervention: Intervention included 7 d treatment with the selective DPP-4 inhibitor vildagliptin or placebo and a standardized test meal on d 7.Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro) insulin, dialysate glucose, lactate, pyruvate, glycerol were measured.Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides, and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptin increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin.Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status. (J Clin Endocrinol Metab 94: 846-852, 2009)