Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean and Obese Subjects

作者：Eldor Roy; Daniele Giuseppe; Huerta Claudia; Al Atrash Mariam; Adams John; DeFronzo Ralph; Duong Timothy; Lancaster John; Zirie Mahmoud; Jayyousi Amin; Abdul Ghani Muhammad^*

来源：Diabetes Care, 2016, 39(10): 1804-1810.

DOI：10.2337/dc15-2706

OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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.

• 出版日期2016-10