Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men
Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men
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DOI：
10.1210/jc.2009-2054
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发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Ahren, Bo
中科院分区：
文献类型：
--
作者：
Carr, Richard D.;Larsen, Marianne O.;Ahren, Bo
背景：葡萄糖依赖型促胰岛素多肽(GIP)和胰高血糖素样肽-1(GLP-1)被二肽基肽酶-4(DPP-4)切割，肥胖患者血浆DPP-4活性可能升高。目的：本研究的目的是评估瘦身和肥胖的非糖尿病受试者的胰岛素分泌和降解。设计、设置和参与者：我们研究了健康瘦肉者(n=12；体重指数，20-25 kg/m(2))和肥胖者(n=13)摄入混合餐(560千卡)或口服葡萄糖(2g/kg)的情况；主要观察指标：测量进食和口服葡萄糖后血浆完整(I)和总(T)GIP和GLP-1的曲线下面积。结果：肥胖组血浆DPP-4活性较高(38.5+/-3.0对26.7+/-1.6 mmol/min)。穆L；P=0.002)。虽然肥胖者进食或口服葡萄糖后GIP分泌量(AUC(TGIP))没有减少，但肥胖者进食后的AUC(IGIP)较低(12.7+/-0.6vs.12.7+/-0.9nmol/L×300min；P<；0.001)。肥胖组GLP-1分泌量(AUC(tglp-1))在进食(7.30±-0.9vs.10.0+/-0.6nmol/L X 300min；P=0.022)和口服葡萄糖(6.6+/-0.8vs.9.6+/-1.1nmol/L X 180min；P=0.035)后均降低。IGLP-1与TGLP-1呈平行下降趋势。结论：1)肥胖时两种胰岛素的释放和降解呈解离变化：餐后GLP-1而不是GIP分泌减少，餐后GIP代谢增加而不是GLP-1代谢增加。2)肥胖患者血浆DPP-4活性的升高与胰岛素代谢的普遍增强无关。(临床内分泌代谢酶95：872-878,2010)
Context: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activity of DPP-4 may be increased in obesity. The impact of this increase on incretin hormone secretion and metabolism is not known.Objective: The aim of the study was to assess incretin hormone secretion and degradation in lean and obese nondiabetic subjects.Design, Settings, and Participants: We studied the ingestion of a mixed meal (560 kcal) or oral glucose (2 g/kg) in healthy lean (n = 12; body mass index, 20-25 kg/m(2)) or obese (n = 13; body mass index, 30-35 kg/m(2)) males at a University Clinical Research Unit.Main Outcome Measures: We measured the area under the curve of plasma intact (i) and total (t) GIP and GLP-1 after meal ingestion and oral glucose.Results: Plasma DPP-4 activity was higher in the obese subjects (38.5 +/- 3.0 vs. 26.7 +/- 1.6 mmol/min . mu l; P = 0.002). Although GIP secretion (AUC(tGIP)) was not reduced in obese subjects after meal ingestion or oral glucose, AUC(iGIP) was lower in obese subjects (8.5 +/- 0.6 vs. 12.7 +/- 0.9 nmol/liter X 300 min; P < 0.001) after meal ingestion. GLP-1 secretion (AUC(tGLP-1)) was reduced in obese subjects after both meal ingestion (7.3 +/- 0.9 vs. 10.0 +/- 0.6 nmol/liter X 300 min; P = 0.022) and oral glucose (6.6 +/- 0.8 vs. 9.6 +/- 1.1 nmol/liter X 180 min; P = 0.035). iGLP-1 was reduced in parallel to tGLP-1.Conclusions: 1) Release and degradation of the two incretin hormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestion and oral glucose, whereas GIP but not GLP-1 metabolism is increased after meal ingestion. 2) Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin hormone metabolism. (J Clin Endocrinol Metab 95: 872-878, 2010)