Effects of substitution of N-terminal amino acid of glucagon-like peptide-1 (7-36) amide on food intake of the neonatal chick

Glucagon-like peptide-1 (GLP-1), a member of glucagon superfamily, is synthesized from a large precursor, preproglucagon, and has been postulated to be a novel incretin. Recently, it was reported that central administration of GLP-1 (7-36) amide decreased food intake in rats and chickens. Generally, the amino acid sequences of the glucagon superfamily members except for gastric inhibitory peptide and growth hormone-releasing factor are identical at N-terminal histidine. It is well known that the GLP-1 receptor is highly specific for GLP-1 and does not bind other peptides of the glucagon superfamily. The aim of this study was to elucidate whether central injection of substituted GLP-1 in which N-terminal histidine of mammalian GLP-1 (7-36) amide was replaced with tyrosine, inhibits food intake in the chick. Intracerebroventricular administration of substituted GLP-1 inhibits food intake in the chick, although the effect of substituted GLP-1 was 11 to 13 fold less than that of mammalian GLP-1 (7-36) amide. These results indicate that N-terminal histidine of GLP-1 (7-36) amide is important for efficacy, but not essential for its bioactivity.