Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance
Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance
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利西拉来通过增加清除率减少乳糜微粒三酰甘油
DOI：
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发表时间：
2018
影响因子：
5.8
通讯作者：
A. Umpleby
中科院分区：
文献类型：
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作者：
M. Whyte;F. Shojaee;S. Sharaf;N. Jackson;B. Fielding;R. Hovorka;J. Mendis;D. Russell;A. Umpleby
胰高血糖素样肽-1（GLP-1）激动剂控制2型糖尿病患者餐后血糖和血脂波动，但其机制尚不清楚。目的探讨利司那肽（GLP-1类似物）对2型糖尿病患者餐后血糖和血脂控制作用的机制。设计：随机、双盲、交叉研究。设置糖尿病，内分泌学和研究中心，皇家萨里县医院，吉尔福德，英国。患者8例肥胖男性2型糖尿病患者[年龄57.3 ± 1.9岁;体重指数30.3 ± 1.0 kg/m2;糖化血红蛋白66.5 ± 2.6 mmol/mol（8.2% ± 0.3%）]。干预两项代谢研究，利司那肽或安慰剂给药后4周，交叉和重复研究。主要结果测量研究一：极低密度脂蛋白（VLDL）和乳糜微粒（CM）三酰甘油（TAG）动力学在12小时的研究中用静脉推注[2 H5]甘油，每小时喂养。单餐中口服[13 C]三油酸甘油酯，标记肠源性TAG。研究二：葡萄糖动力学用[U-13 C]葡萄糖在混合膳食（加上对乙酰氨基酚以测量胃排空）和可变IV [6，6 - 2 H2]葡萄糖输注中测量。结果研究1：利司那肽组的CM-TAG（而非VLDL-TAG）合并量较低（P = 0.046）。利多卡因降低了CM [13 C]油酸酯60- 480 min浓度曲线下面积（AUC）（P = 0.048），并增加了CM-TAG清除率，对CM-TAG产生速率无影响。研究二：利司那肽组餐后血糖和胰岛素AUC 0 - 240 min降低（P = 0.0051; P < 0.05）。利司那肽组的总葡萄糖生成（P = 0.015）、餐后葡萄糖出现率（P = 0.0098）和对乙酰氨基酚AUC 0 - 360 min（P = 0.006）低于安慰剂组。结论利多卡因通过延迟胃排空降低CM-TAG中来自单餐的[13 C]油酸浓度和餐后葡萄糖出现率。然而，利司那肽未降低通过重复进食测量的全天CM产生，CM-TAG清除率增加导致CM-TAG浓度降低。
Abstract Context Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. Objective To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. Design Randomized, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Patients Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. Interventions Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. Main Outcome Measures Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60–480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0–240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0–360min (P = 0.006) were lower with lixisenatide than with placebo. Conclusions Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.
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DOI：
10.1161/01.atv.15.12.2122
发表时间：
1995-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
A. Sharrett;L. Chambless;G. Heiss;C. Paton;W. Patsch
通讯作者：
A. Sharrett;L. Chambless;G. Heiss;C. Paton;W. Patsch
DOI：
10.1152/ajpendo.00205.2016
发表时间：
2016-09-01
影响因子：
5.1
作者：
Chai, Weidong;Fu, Zhuo;Liu, Zhenqi
通讯作者：
Liu, Zhenqi
影响因子：
7.7
作者：
Vella, A;Shah, P;Rizza, RA
通讯作者：
Rizza, RA
胰高血糖素样肽-1受体激动剂利西拉来对清醒狗餐后肝脏葡萄糖代谢的影响。
DOI：
10.1152/ajpendo.00354.2013
发表时间：
2013
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Moore,MaryCourtney;Werner,Ulrich;Smith,MartaS;Farmer,TiffanyD;Cherrington,AlanD
通讯作者：
Cherrington,AlanD