Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects
Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects
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DOI：
10.1016/j.diabres.2007.08.001
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发表时间：
2008-01-01
影响因子：
5.1
通讯作者：
Flatt, Peter R.
中科院分区：
文献类型：
--
作者：
McKillop, Aine M.;Duffy, Nicola A.;Flatt, Peter R.
二肽基肽酶（DPP-IV）快速代谢激素如胰高血糖素样肽-1（7-36）酰胺。本研究评价了2型糖尿病患者中与GLP-1降解和代谢控制相关的循环DPP-IV活性。从3个主要类别的2型糖尿病患者中采集血样：良好的血糖控制（HbA（1c）9%）。年龄和性别匹配的非糖尿病受试者作为对照。健康对照受试者的循环DPP-IV活性为22.5 ± 0.7 nmol/ml/min（n = 70）。在2型糖尿病受试者的联合组中，循环DPP-IV活性显著降低至18.1 +/- 0.7 nmol/ml/min（p < 0.001，n = 54）。在该人群中，DPP-IV活性与血糖（p < 0.01）和HbA（1c）（p < 0.01）呈负相关。此外，DPP-IV活性降低1.2倍（p < 0.01，n = 25），1.3倍（p < 0.001，n = 19）和1.3倍（p < 0.05，n =10）在良好、中度和不良控制的糖尿病组中，分别为18.7 +/- 1.0、17.4 +/- 1.4和18.0 +/- 1.5 nmol/ml/min。通过与来自健康和2型糖尿病受试者的合并血浆样品体外孵育的GLP-1降解显示，糖尿病组中无活性代谢物GLP-1（9-36）的降解降低。这些数据表明2型糖尿病中DPP-IV活性和GLP-1降解降低。DPP-IV酶活性似乎是抑郁症控制不良的反应。（c）. 2007爱思唯尔爱尔兰有限公司保留所有权利。
Dipeptidyl peptidase (DPP-IV) rapidly metabolises hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) 9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5 +/- 0.7 nmol/ml/min (n = 70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1 +/- 0.7 nmol/ml/min (p < 0.001, n = 54). DPP-IV activity was negatively correlated with both glucose (p < 0.01) and HbA(1c) (p < 0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p < 0.01, n = 25), 1.3-fold (p < 0.001, n = 19) and 1.3-fold (p < 0.05, n =10) in good, moderate and poorly controlled diabetic groups, 18.7 +/- 1.0, 17.4 +/- 1.4 and 18.0 +/- 1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control. (c). 2007 Elsevier Ireland Ltd. All rights reserved.