Eldor Roy, Daniele Giuseppe, Huerta Claudia, Al-Atrash Mariam, Adams John, DeFronzo Ralph, Duong Timothy, Lancaster John, Zirie Mahmoud, Jayyousi Amin, Abdul-Ghani Muhammad
Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Imaging Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Diabetes Care. 2016 Oct;39(10):1804-10. doi: 10.2337/dc15-2706. Epub 2016 Aug 3.
This study examined the effect of exenatide on brain activity measured by functional (f)MRI and on insulin secretion in lean and obese normal-glucose-tolerant individuals.
The brain fMRI signal in response to high-calorie-content food pictures was measured with and without intravenous exenatide infusion in 10 lean and 10 obese healthy volunteers. Insulin secretion was measured with a two-step (+100 and +200 mg/dL) hyperglycemic clamp with exenatide and with saline infusion.
The brain fMRI signal in response to food pictures in amygdala, insula, hippocampus, and frontal cortex was significantly greater in obese versus lean individuals. Intravenous exenatide significantly inhibited the fMRI signal in response to food pictures in obese individuals but did not affect the brain fMRI signal in lean subjects. Conversely, exenatide infusion caused an 18.5-fold increase in insulin secretion in lean individuals compared with an 8.8-fold increase in obese subjects. No significant correlation was observed between inhibition of the brain fMRI signal and increase in insulin secretion during exenatide infusion.
Exenatide causes greater augmentation in insulin secretion in lean compared with obese individuals but inhibits the brain response to food pictures only in obese individuals.
本研究检测了艾塞那肽对通过功能磁共振成像（fMRI）测量的脑活动以及对体重正常和肥胖的糖耐量正常个体胰岛素分泌的影响。
在10名体重正常和10名肥胖的健康志愿者中，分别在静脉输注艾塞那肽前后测量其对高热量食物图片产生反应时的脑fMRI信号。采用两步法（+100和+200mg/dL）高血糖钳夹技术，分别在输注艾塞那肽和生理盐水时测量胰岛素分泌情况。
与体重正常个体相比，肥胖个体杏仁核、脑岛、海马体和额叶皮质对食物图片产生反应时的脑fMRI信号显著增强。静脉注射艾塞那肽显著抑制了肥胖个体对食物图片产生反应时的fMRI信号，但对体重正常个体的脑fMRI信号无影响。相反，与肥胖个体增加8.8倍相比，输注艾塞那肽使体重正常个体的胰岛素分泌增加了18.5倍。在输注艾塞那肽期间，未观察到脑fMRI信号抑制与胰岛素分泌增加之间存在显著相关性。
与肥胖个体相比，艾塞那肽使体重正常个体的胰岛素分泌增加幅度更大，但仅抑制肥胖个体对食物图片的脑反应。
