title: Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean and Obese Subjects.
abstract: 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.
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Roy
authors.initials: R
authors.lastname: Eldor
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daniele
authors.affiliation: Imaging Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Claudia
authors.initials: C
authors.lastname: Huerta
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Mariam
authors.initials: M
authors.lastname: Al-Atrash
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: John
authors.initials: J
authors.lastname: Adams
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Ralph
authors.initials: R
authors.lastname: DeFronzo
authors.affiliation: Imaging Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Timothy
authors.initials: T
authors.lastname: Duong
authors.affiliation: Imaging Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: John
authors.initials: J
authors.lastname: Lancaster
authors.affiliation: Diabetes and Obesity Clinical Research Center, Hamad General Hospital, Doha, Qatar.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Zirie
authors.affiliation: Diabetes and Obesity Clinical Research Center, Hamad General Hospital, Doha, Qatar.
authors.forename: Amin
authors.initials: A
authors.lastname: Jayyousi
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX abdulghani@uthscsa.edu.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abdul-Ghani
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage*; D014688:Venoms / Q000008:administration & dosage*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists