AIM To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin on glycaemic and energy expenditure responses during intraduodenal fat infusion, as well as the contribution of endogenous glucagon-like peptide-1 (GLP-1) signalling, in people with type 2 diabetes (T2DM). METHODS A total of 15 people with T2DM managed by diet and/or metformin (glycated haemoglobin 49.3 ± 2.1 mmol/mol) were studied on three occasions (two with vildagliptin and one with placebo) in a double-blind, randomized, crossover fashion. On each day, vildagliptin 50 mg or placebo was given orally, followed by intravenous exendin (9-39) 600 pmol/kg/min, on one of the two vildagliptin treatment days, or 0.9% saline over 180 minutes. At between 0 and 120 minutes, a fat emulsion was infused intraduodenally at 2 kcal/min. Energy expenditure, plasma glucose and glucose-regulatory hormones were evaluated. RESULTS Intraduodenal fat increased plasma GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P < 0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP-1 was higher (all P < 0.05), and energy expenditure tended to be lower after vildagliptin (P = 0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP-1 (both total and intact), and energy expenditure were higher during intravenous exendin (9-39) than saline (all P < 0.05). CONCLUSIONS In well-controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP-1.

中文翻译：

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维格列汀增强内源性胰高血糖素样肽1在2型糖尿病对十二指肠内脂肪输注的血糖和能量消耗反应中的作用。

目的评估二肽基肽酶-4（DPP-4）抑制剂维格列汀对十二指肠内脂肪输注过程中血糖和能量消耗反应的影响，以及内源性胰高血糖素样肽-1（GLP-1）信号传导的作用。 2型糖尿病（T2DM）人群。方法共有15例通过饮食和/或二甲双胍（糖化血红蛋白为49.3±2.1 mmol / mol）管理的2型糖尿病患者，以双盲，随机，交叉的方式研究了三种情况（两次使用维达列汀治疗，另一次使用安慰剂治疗）。每天口服维达列汀50 mg或安慰剂，然后在两个维达列汀治疗日之一内静脉滴加exendin（9-39）600 pmol / kg / min，或在180分钟内给予0.9％的盐水。在0-120分钟之间，以2 kcal / min的剂量将脂肪乳剂十二指肠内注入。能量消耗，评估血浆葡萄糖和葡萄糖调节激素。结果十二指肠内脂肪增加血浆GLP-1和葡萄糖依赖性促胰岛素多肽（GIP），胰岛素和胰高血糖素以及能量消耗，并降低血浆葡萄糖（所有P <0.05）。在静脉注射生理盐水的两天中，维格列汀治疗后血浆葡萄糖和胰高血糖素较低，血浆完整GLP-1较高（所有P <0.05），能量消耗往往比安慰剂低（P = 0.08）。在维格列汀的两天中，静脉内艾迪生（9-39）期间血浆葡萄糖，胰高血糖素和GLP-1（总量和完整）和能量消耗均高于生理盐水（所有P <0.05）。结论在十二指肠内输注期间，在控制良好的T2DM中，维格列汀可降低血浆葡萄糖和胰高血糖素，并倾向于减少能量消耗，