Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates

Nicholas T. Bello, Matthew H. Kemm, Erica M. Ofeldt, Timothy H. Moran

Research output: Contribution to journalArticlepeer-review

Abstract

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 μg/kg), sCT (0, 0.1, or 0.32 μg/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 μg/kg Ex-4 + 0.32 μg/kg sCT for 5 days. This resulted in sustained reductions in daily food intake (>70% from saline baseline) for 5 days with residual reductions (∼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 (∼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.

Original languageEnglish (US)
Pages (from-to)R945-R952
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number3
DOIs
StatePublished - Sep 2010

Keywords

  • Exenatide
  • Gut peptides
  • Islet amyloid polypeptide
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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