Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System
Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System
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DOI：
10.2337/db14-1718
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发表时间：
2015-10-01
期刊：
影响因子：
7.7
通讯作者：
Gastaldelli, Amalia
中科院分区：
文献类型：
--
作者：
Daniele, Giuseppe;Iozzo, Patricia;Gastaldelli, Amalia
胰高血糖素样肽1受体（GLP-1 Rs）已在脑中发现，但GLP-1 R激动剂（GLP-1 RA）是否影响脑葡萄糖代谢目前尚不清楚。本研究旨在评价单次注射GLP-1 RA外消旋体对葡萄糖负荷后大脑和外周葡萄糖代谢的影响。在15名男性受试者中，HbA（1c）为5.7 +/-0.1%，空腹血糖为114 +/- 3 mg/dL，2小时血糖为177 +/- 11 mg/dL，在口服葡萄糖耐量试验（OGTT）前30分钟以双盲、随机方式皮下注射艾塞那肽（5 μ g）或安慰剂。在OGTT前注射[F-18]2-氟-2-脱氧-D-葡萄糖后，通过正电子发射断层扫描测量脑葡萄糖代谢率（CMRglu），并使用稳定同位素示踪剂评估葡萄糖吸收率（RaO）和处置率。艾塞那肽降低RaO 0 -60 min（4.6 +/- 1.4 vs. 13.1 +/- 1.7 μ mol/min）。kg），并降低平均葡萄糖（0-60）（min）（107 +/- 6 vs. 138 +/- 8 mg/dL）和胰岛素（0-60）（min）（17.3 +/- 3.1 vs. 24.7 +/- 3.8 mU/L）的升高。尽管血浆胰岛素浓度较低，艾塞那肽增加了与葡萄糖稳态、食欲和食物奖励相关的大脑区域中的CMRglu，但减少了下丘脑中的葡萄糖摄取。exenglutamine后Ra 0 -60（min）的降低与CMRglu呈负相关。总之，这些结果首次在人体中证明了GLP-1 RA对吸收状态下脑葡萄糖代谢调节的主要作用。
Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA(1c) of 5.7 +/- 0.1%, fasting glucose of 114 +/- 3 mg/dL, and 2-h glucose of 177 +/- 11 mg/dL, exenatide (5 mu g) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [F-18]2-fluoro-2-deoxy-D-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 +/- 1.4 vs. 13.1 +/- 1.7 mu mol/min . kg) and decreased the rise in mean glucose(0-60) (min) (107 +/- 6 vs. 138 +/- 8 mg/dL) and insulin(0-60) (min) (17.3 +/- 3.1 vs. 24.7 +/- 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased Ra0-60 (min) after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.