title: Actions of incretin metabolites on locomotor activity, cognitive function and in vivo hippocampal synaptic plasticity in high fat fed mice.
abstract: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity-diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9-36)amide and GIP(3-42), respectively. Therefore, the present study investigated effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive function and hippocampal synaptic plasticity in mice with diet-induced obesity and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide, GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any changes in bodyweight, non-fasting plasma glucose and plasma insulin concentrations or glucose tolerance compared with high-fat saline controls. Similarly, locomotor and feeding activity, O(2) consumption, CO(2) production, respiratory exchange ratio and energy expenditure were not altered by chronic treatment with incretin metabolites. Administration of the truncated metabolites did not alter general behavior in an open field test or learning and memory ability as recorded during an object recognition test. High-fat mice exhibited a significant impairment in hippocampal long-term potentiation (LTP) which was not affected by treatment with incretin metabolites. These data indicate that incretin metabolites do not influence locomotor activity, cognitive function and hippocampal synaptic plasticity when administered at pharmacological doses to mice fed a high-fat diet.
authors.affiliation: The SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Porter
authors.forename: Emilie
authors.initials: E
authors.lastname: Faivre
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
authors.forename: Victor A
authors.initials: VA
authors.lastname: Gault
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D005247:Feeding Behavior / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D054795:Incretins / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects
chemical_list: D054795:Incretins; D010446:Peptide Fragments; D010455:Peptides; C515715:gastric inhibitory polypeptide (3-42); C114437:glucagon-like peptide-1 (9-36)-amide; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1