Stimulation of insulin release and potentiation of the insulinotropic action of antidiabetic agents by 1,2,3-tri(methylsuccinyl)glycerol ester in anaesthetized rats.
A novel ester of succinic acid (1,2,3-tri(methylsuccinyl)glycerol ester; 3SMG) was found to stimulate insulin release and to potentiate the insulinotropic action of gliquidone and repaglinide when administered intravenously to normal anaesthetized rats in a dose as low as 0.07 mumol g-1 body wt. The ester failed, however, to augment plasma insulin concentration when given enterally. The design of succinic acid esters of high insulinotropic potential might thus allow efficient stimulation of insulin secretion in non-insulin-dependent diabetes, without requiring unpractical high dosage and without running the risk of an undesirable increase in gluconeogenesis.
García-Martínez
J A
JA
Fundación Jíménez Díaz, Madrid, Spain.
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Björkling
F
F
Malaisse
W J
WJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology; D004357:Drug Synergism; D004952:Esters / Q000008:administration & dosage / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology
C109543:1,2,3-tri(methylsuccinyl)glycerol ester; D001786:Blood Glucose; D002219:Carbamates; D004952:Esters; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D013386:Succinates; D013453:Sulfonylurea Compounds; C072379:repaglinide; C010969:gliquidone