Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates.
Glucagon-like peptide-1 (GLP-1) and amylin mediate the feedback control of eating by seemingly separate, but overlapping mechanisms. This study examined the effects of combined doses of the GLP-1 agonist, exendin-4 (Ex-4), and the amylin analog, salmon calcitonin (sCT), on food intake and meal patterns in adult male rhesus monkeys. Monkeys received intramuscular injections of Ex-4 (0, 0.1, 0.32, or 0.56 microg/kg), sCT (0, 0.1, or 0.32 microg/kg), or combinations thereof before a 6-h daily access to food. Dose combinations produced reductions in food intake that were significantly greater than those produced by the individual doses. Surface plots of the hourly intake indicated a synergistic interaction at lower doses of Ex-4 and sCT during the first 4 h of feeding and additive effects at hours 5 and 6. Meal pattern analysis revealed the combinational doses reduced average meal size and meal frequency by additive interactions, whereas infra-additive effects were apparent at lower doses for first meal size. Combinational doses were further characterized by administration of repeated daily injections of 0.56 microg/kg Ex-4 + 0.32 microg/kg sCT for 5 days. This resulted in sustained reductions in daily food intake (>70% from saline baseline) for 5 days with residual reductions ( approximately 48% from saline baseline) persisting on day 1 following the injections. In contrast, when pair-fed an identical amount of daily food, there was a compensatory food intake increase on day 1 following the pair-feeding ( approximately 132% of saline baseline). Such data suggest Ex-4 and sCT interact in an overall additive fashion to reduce food intake and further the understanding of how GLP-1 and amylin agonist combinations influence feeding behavior.
Bello
Nicholas T
NT
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Univ. School of Medicine, Baltimore, MD 21205, USA.
Kemm
Matthew H
MH
Ofeldt
Erica M
EM
Moran
Timothy H
TH
D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
D010455:Peptides; D014688:Venoms; C028815:salmon calcitonin; D002116:Calcitonin; D000077270:Exenatide