Stimulation of insulin secretion and potentiation of glibenclamide-induced insulin release by the dimethyl ester of glutamic acid in anaesthetized rats.
The dimethyl ester of L-glutamic acid (GME) stimulates insulin release in isolated pancreatic islets and may represent a novel experimental tool in the study of non-insulin-dependent diabetes. In the present study, GME was found both to stimulate insulin secretion and to augment glibenclamide-stimulated insulin release in normal anaesthetized rats. A comparable hierarchy in the magnitude of the secretory response to GME and/or glibenclamide was found in control rats and animals injected with streptozotocin during the neonatal period. In the latter animals, however, the B-cell secretory response was invariably lower than in control animals. It is proposed that GME represents a novel tool to bypass anomalies of glucose transport and metabolism in the beta cell and, hence, to stimulate insulin release and enhance the insulinotropic action of hypoglycaemic sulphonylurea in animal models of non-insulin-dependent diabetes.
Vicent
D
D
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Garcia-Martinez
J A
JA
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Malaisse
W J
WJ
D000768:Anesthesia, General; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004357:Drug Synergism; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D005971:Glutamates; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; C035873:glutamic acid dimethyl ester; D005905:Glyburide