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首页> 外文期刊>Diabetic medicine: A journal of the British Diabetic Association >Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes.
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Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes.

机译：口服二甲双胍对2型糖尿病患者二肽基肽酶-4（DPP-4）活性的影响研究。

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AIMS: Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone and major component of the enteroinsular axis. Its therapeutic potential in human diabetes is limited by rapid degradation and inactivation by the enzyme dipeptidylpeptidase-4 (DPP-4). We investigated the acute effects of metformin with and without food on DPP-4 activity in Type 2 diabetes. METHODS: Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m2, glycated haemoglobin (HbA(1c)) 6.3 +/- 0.2%, mean +/- SEM) received metformin 1 g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects re-attended fasting and received metformin 1 g without a SMM. RESULTS: Following SMM (n = 10), DPP-4 activity was not suppressed by metformin compared with placebo [area under curve (AUC)(0-4 h) 1574 +/- 4 vs. 1581 +/- 8 micromol/ml/min, respectively]. Plasma glucose, insulin and active GLP-1 were not different. However, DPP-4 activity was suppressed with metformin following fasting compared with a SMM (n = 6) (AUC(0-4 h) 1578 +/- 4 vs. 1494 +/- 9 micromol/min, P < 0.02). Metformin serum levels were significantly lower (P < 0.001) after SMM than fasting (AUC(0-4 h) 350 +/- 66 vs. 457 +/- 55 mg/ml/min). CONCLUSION: Metformin inhibits DPP-4 activity in Type 2 diabetic patients in the fasting state but not when taken with a standard mixed meal. Metformin serum concentrations are lower if the drug is taken with food. These findings should be taken into account in establishing how to maximize efficacy of the drug.
机译：目的：胰高血糖素样肽-1（GLP-1）是促胰岛素激素，是肠小肠轴的主要成分。它在人类糖尿病中的治疗潜力受到二肽基肽酶-4（DPP-4）酶的快速降解和失活的限制。我们调查了有和没有食物的二甲双胍对2型糖尿病DPP-4活性的急性影响。方法：十名2型糖尿病患者（6名男性/ 4名女性，年龄65.8 +/- 2.6岁，体重指数30.0 +/- 1.2 kg / m2，糖化血红蛋白（HbA（1c））6.3 +/- 0.2％，平均+/- SEM）以随机分频设计口服1 g二甲双胍或安慰剂以及标准混合餐（SMM）。六名受试者重新禁食并接受了1 g无SMM的二甲双胍。结果：在SMM（n = 10）之后，与安慰剂相比，二甲双胍未抑制DPP-4活性[曲线下面积（AUC）（0-4 h）1574 +/- 4与1581 +/- 8 micromol / ml / min]。血浆葡萄糖，胰岛素和活性GLP-1并无差异。然而，与SMM（n = 6）相比，禁食后二甲双胍抑制了DPP-4活性（AUC（0-4 h）1578 +/- 4 vs. 1494 +/- 9 micromol / min，P <0.02）。 SMM后的二甲双胍血清水平显着低于禁食（AUC（0-4 h）350 +/- 66 vs.457 +/- 55 mg / ml / min）（P <0.001）。结论：二甲双胍在空腹状态下可抑制2型糖尿病患者的DPP-4活性，但与标准混合餐一起服用时则不能。如果与食物一起服用，二甲双胍的血清浓度会降低。在确定如何最大程度地发挥药物功效时应考虑这些发现。

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