Insulinotropic action of the D-glucosyl and 3-O-methyl-D-glucosyl monomethyl esters of succinic acid.
Succinic acid methyl esters are currently under investigation as potential insulinotropic tools in animal models of non-insulin-dependent diabetes mellitus. The in vivo administration of these esters may result in the undesirable generation of methanol through their intracellular hydrolysis. As a first attempt to circumvert this drawback, we have now investigated whether the esterification of the carboxylic group of succinic acid monomethyl ester by D-glucose or 3-O-methyl-D-glucose affects its insulin-otropic action. Both the 6-O-D-glucosyl and 6-O-(3-O-methyl)-D-glucosyl esters were found to stimulate insulin release in pancreatic islets and the isolated perfused pancreas. The 6-O-D-glucosyl ester also stimulated insulin release after intravenous administration to anaesthetized rats. These findings suggest that the undersirable generation of methanol from the methyl esters of succinic acid could eventually be avoided by using other esters of this dicarboxylic acid, whilst keeping the benefit of their insulinotropic action.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Erasmus Medical School, Belgium.
Zhang
T M
TM
Leclercq-Meyer
V
V
Sener
A
A
Björkling
F
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D010179:Pancreas / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D001786:Blood Glucose; D004952:Esters; D007328:Insulin; D013386:Succinates; D005934:Glucagon; D005947:Glucose; D005905:Glyburide; C041105:monomethyl succinate