The central actions of the glucagon-like peptide-1 receptor agonist, exendin-4, in Suncus murinus: A telemetric study

Abstract

Introduction. GLP-1 receptor agonists for the treatment of type 2 diabetes can be associated with nausea, emesis and reduced appetite in man. The GLP-1 receptor agonist, exendin-4, inhibits feeding and water intake, and induces emesis in Suncus murinus.

Aims. The aim of this study is to investigate the central actions of GLP-1 receptor agonist, exendin-4 by using radiotelemetry in Suncus murinus.

Methods. A guide cannula was implanted into the lateral ventricle under anesthesia. After seven days, two biopotential wires of a telemetric transmitter were implanted into the antrum and its pressure catheter was implanted into the left carotid artery under anesthesia. After seven days recovery, baseline recordings were made for 12 h before exendin-4 (0.03, 0.3 and 3 nmol, i.c.v.) or saline (5 μl, i.c.v.) injection. Behavioral observation and telemetric recordings were continued for a further 24 h.

Results. Central administration of exendin-4 significantly inhibited food and water intake at 4-5 h and 5-24 h post-injection, and also prevented 24 h body weight gain; these effects were dose-related. In addition, exendin-4 also dose-dependently induced emesis. The telemetric recordings showed that exendin-4 increased systolic and diastolic blood pressure, and increased heart rate and body temperature during the first 4 h following injection. Exendin-4 at 0.3 and 3 nmol, i.c.v., also significantly increased the dominant frequency of gastric slow waves during the first 4 h.

Conclusions. This study showed that central GLP-1 receptors may be important in emesis control, food and water intake, and the modulation of cardiovascular function and gastric slow waves. The studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/15).