Synergistic insulinotropic effects of succinic acid dimethyl ester and exendin-4 in anaesthetized rats.
It was recently proposed that suitable succinic acid esters could be used to potentiate the insulinotropic action of glucagon-like peptide 1 (GLP-1) in the treatment of type-2 diabetes mellitus. In such a perspective, the present study aimed mainly at investigating whether exendin-4 (Ex-4), a peptide structurally related to GLP-1(7-36)amide, and succinic acid dimethyl ester (SAD) also act synergistically upon insulin secretion in anaesthetized rats. Despite a higher plasma insulin concentration in SAD-infused rats (5.5+/-1.1 ng/ml) than in saline-infused animals (1.9+/-0.7 ng/ml), the intravenous injection of Ex-4 augmented to a greater extent the plasma concentration of insulin in the former rats (+7.4+/-2.5 ng/ml) than in the latter animals (+2.8+/-0.6 ng/ml). These findings document that the insulinotropic actions of Ex-4 and GLP-1 display comparable nutrient dependency, being both potentiated by a non-glucidic nutrient secretagogue such as SAD.
Cancelas
J
J
Fundacion Jimenez Diaz, 28040 Madrid, Spain.
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Malaisse
W J
WJ
D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D000077270:Exenatide; D007328:Insulin / Q000097:blood*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000494:pharmacology*; D013997:Time Factors; D014688:Venoms
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D013386:Succinates; D014688:Venoms; C056451:dimethyl succinate; D000077270:Exenatide