Potentiation of the insulinotropic action of GLP-1 by succinic acid dimethyl ester in fed anaesthetized rats.
The insulinotropic action of GLP-1 is modulated by the nutritional environment of islet B-cells. This study explores whether an ester of succinic acid could be used to potentiate the insulin secretory response to GLP-1 in vivo. Fed anaesthetized male rats received a primed constant infusion (0.5 micromol followed by 0.25 micromol x min(-1) both per g body wt) of succinic acid dimethyl ester (SAD) in saline for 15 min and, at the 5th min of such an infusion, an intravenous injection of GLP-1 (5 pmol/g body wt). The ester provoked a rapid, sustained and reversible increase in plasma insulin concentration. In the SAD-infused rats, the increment in plasma insulin concentration caused by GLP-1 was more pronounced and more sustained than in saline-infused rats. It is proposed, therefore, that suitable succinic acid esters could be used to potentiate the insulinotropic action of GLP-1 in Type II (non-insulin-dependent) diabetes.
García-Martínez
J A
JA
Fundació6n Jiménez Diaz, Madrid, Spain.
Cancelas
J
J
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Malaisse
W J
WJ
D000818:Animals; D004357:Drug Synergism; D005502:Food; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D013386:Succinates; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C056451:dimethyl succinate