Insulinotropic action of 1,2,3-Tri(methylsuccinyl)glycerol ester.
A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol ester (3SMG), was found to stimulate insulin release from rat pancreatic islets. In the presence of 7 mM d-glucose, a 10 microM concentration of 3SMG was sufficient to cause a significant increase in insulin output. The ester mimicked the effect of other nutrient secretagogues in enhancing the synthesis of islet peptides, with a preferential action on proinsulin as distinct from nonhormonal peptides, in decreasing 86Rb outflow from prelabeled islets, and in stimulating Ca2+ inflow into the islet cells. It is proposed, therefore, that 3SMG displays the attributes suitable for stimulation or potentiation of insulin release in noninsulin-dependent diabetes, without requiring administration in large amounts and, hence, without the risk of excessive hepatic gluconeogenesis.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Ladrière
L
L
Laghmich
A
A
Louchami
K
K
Jijakli
H
H
Viñambres
C
C
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Björkling
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology*
C109543:1,2,3-tri(methylsuccinyl)glycerol ester; D004952:Esters; D007328:Insulin; D012414:Rubidium Radioisotopes; D013386:Succinates; D010649:Phenylalanine; D002118:Calcium