Evidence for a direct stimulatory effect of cibenzoline on insulin secretion in rats.
The effect of cibenzoline succinate, a new antiarrhythmic agent, was studied on insulin secretion in rats. Experiments were performed both in vivo and in vitro using two preparations: the isolated perfused pancreas and isolated islets. In anaesthetized rats, cibenzoline was able to increase plasma insulin levels and to reduce glycaemia. These effects were observed at 1 mg/kg i.v. in fed rats and at 3 mg/kg i.v. in fasted rats. In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration-dependent manner. In the presence of a non-stimulating glucose concentration (4.2 mM), cibenzoline was ineffective at 2 microM and slightly increased basal insulin release at 6 microM. In isolated islets incubated with 8.3 mM glucose, cibenzoline (6 and 20 microM) caused a concentration-dependent stimulation of insulin release. It is concluded that cibenzoline stimulates insulin secretion by a direct action on pancreatic B cells in rats.
Bertrand
G
G
Centre CNRS INSERM de Pharmacologie-Endocrinologie UMR 6, Montpellier, France.
Gross
R
R
Petit
P
P
Loubatières-Mariani
M M
MM
Ribes
G
G
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity; D001786:Blood Glucose / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced; D007093:Imidazoles / Q000633:toxicity*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; C032151:cifenline