Effect of the meglitinide analog S21403 on cationic fluxes and insulin release in perifused rat pancreatic islets exposed to a high concentration of D-glucose.
The effect of the meglitinide analog S21403 (10 microm) upon(86)Rb and(45)Ca outflow and insulin release was investigated in perifused rat islets exposed to a high concentration of D-glucose (16.7 mm) in order to simulate the situation found in diabetic patients. Under these conditions, S21403 provoked a rapid, sustained and rapidly reversible increase in(86)Rb outflow, (45)Ca efflux and insulin release. These effects were suppressed or reversed when the experiments were conducted in the absence of extracellular Ca2+. They support the view that S21043 could be used as a novel insulinotropic tool in the treatment of non-insulin-dependent diabetes mellitus, the cationic and secretory responses to the drug displaying a favourable time course for prompt and not unduly prolonged activation of islet B-cells.
Louchami
K
K
Laboratory of Experimental Medicine, Brussels Free University, 808 Route de Lennik, Brussels, B-1070, Belgium.
Jijakli
H
H
Malaisse
W J
WJ
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics*; D002132:Calcium Radioisotopes; D002412:Cations; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D054833:Isoindoles; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000493:pharmacokinetics*; D012414:Rubidium Radioisotopes
D002132:Calcium Radioisotopes; D002412:Cations; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D054833:Isoindoles; D012414:Rubidium Radioisotopes; C087255:mitiglinide; D005947:Glucose; D012413:Rubidium; D002118:Calcium