title: Increased food intake with oxyntomodulin analogues.
abstract: Oxyntomodulin analogues offer a novel treatment for obesity. However during analogue screening in a rat model increased food intake was consistently observed. To further investigate this finding, a series of representative analogues (OXM14 and OXM15) and their Glu-3 equivalents (OXM14E3 and OXM15E3) were administered to rats for 7 days and food intake and bodyweight measurements taken. To investigate the role of glucagon receptor activation glutamate (Glu/E) was substituted at amino acid position 3. GLP-1 and glucagon receptor efficacy of the oxyntomodulin analogues and their Glu-3 counterparts were measured at the rat receptors in vitro. Doses of 25 nmol/kg of OXM14 and OXM15 increased food intake by up to 20%. Bodyweight was not significantly increased. Food intake was not increased with the Glu-3 peptides, indicating that a glucagon receptor mechanism may be responsible for the increase in food intake.
authors.affiliation: Department of Investigative Medicine, Imperial College, London W12 0NN, United Kingdom.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Price
authors.affiliation: Department of Investigative Medicine, Imperial College, London W12 0NN, United Kingdom.
authors.forename: James S
authors.initials: JS
authors.lastname: Minnion
authors.affiliation: Department of Investigative Medicine, Imperial College, London W12 0NN, United Kingdom. Electronic address: s.bloom@imperial.ac.uk.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004435:Eating / Q000187:drug effects*; D008297:Male; D053772:Oxyntomodulin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053772:Oxyntomodulin
keywords: GLP-1; Glucagon; Oxyntomodulin; cAMP