Discordance between central (Brain) and pancreatic action of exenatide in lean and obese subjects

Roy Eldor, Giuseppe Daniele, Claudia Huerta, Mariam Al-Atrash, John Adams, Ralph De Fronzo, Timothy Duong, John Lancaster, Mahmoud Zirie, Amin Jayyousi, Muhammad Abdulghani

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1804-1810
Number of pages7
JournalDiabetes care
Volume39
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016

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