Enhancement by succinic acid dimethyl ester of insulin release evoked by D-glucose and glimepiride in the perfused pancreas of normoglycemic and hyperglycemic rats.
The present study deals with the insulinotropic action of the dimethyl ester of succinic acid (SAD), considered as a potential tool for the treatment of non-insulin-dependent diabetes mellitus. In the perfused pancreas prepared from either euglycemic rats or animals first infused for 48 hours with a solution of D-glucose, SAD (10 mM) markedly enhanced insulin output evoked by a high concentration of D-glucose (16.7 mM), whether in the absence or presence of glimepiride (0.5 microM). The succinate ester failed, however, to affect glucagon secretion. Thus, SAD indeed displays favourable attributes for stimulation of insulin release in type 2 diabetes, with emphasis on its insulinotropic efficiency at high concentrations of D-glucose in an animal model of B-cell glucotoxicity.
Leclercq-Meyer
V
V
Laboratory of Experimental Medicine, Erasmus School of Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004357:Drug Synergism; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D013386:Succinates; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005934:Glucagon; C056451:dimethyl succinate; D005947:Glucose