Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats.
Glucagon-like peptide-1(7-36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5-170 pmol.kg(-1).min(-1)) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol.kg(-1).min(-1) and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7-50 pmol.kg(-1).min(-1)) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol.kg(-1).min(-1) and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5-50 pmol.kg(-1).min(-1)) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.
Chelikani
Prasanth K
PK
Department of Veterans Affairs Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA.
Haver
Alvin C
AC
Reidelberger
Roger D
RD
D000818:Animals; D001067:Appetite Depressants; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects*; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000187:drug effects
D001067:Appetite Depressants; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon