Glucose modulates the amount, but not the kinetics, of insulin released by sulfonylureas.
This study compares the insulin-secretory profiles induced by therapeutical concentrations of four different sulfonylureas--tolbutamide, gliquidone, gliclazide, and glibenclamide--and the amount of hormone released by each under different ambient glucose concentrations, using the isolated perfused rat pancreas model. All four sulfonylureas stimulated B-cell function, but the kinetics varied. Tolbutamide, gliquidone, and gliclazide produced a quick, biphasic release, whereas glibenclamide stimulated a delayed monophasic insulin secretion. Dramatic falls in insulin release were observed when ambient glucose concentrations were lowered. Glucagon release was not influenced by any of the sulfonylureas whatever the metabolic condition, neither directly nor indirectly, via an insulin-mediated paracrine inhibition of A-cell activity.
Dipartimento di Medicina Clinica, Patologia e Farmacologia, Universitá degli Studi di Perugia, Italy.
F
F
Gregorio
F
F
Ambrosi
P
P
Filipponi
S
S
Cristallini
F
F
Santeusanio
D000818:Animals; D005907:Gliclazide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D014044:Tolbutamide; C010969:gliquidone; D005907:Gliclazide; D005947:Glucose; D005905:Glyburide