Comparison of the cationic and secretory response of pancreatic islets to gliclazide and/or potassium.
The concept that hypoglycemic sulfonylureas stimulate Ca2+ inflow and insulin release in the pancreatic B-cell by causing the gating of voltage-sensitive Ca2+ channels was tested by comparing the cationic and secretory response of perifused pancreatic islets to gliclazide and/or an increase in extracellular K+ concentration. In the presence of glucose (2.8 mM), both procedures resulted in an immediate and sustained stimulation of 45Ca and insulin release from prelabelled islets. The capacity of gliclazide to stimulate 45Ca and insulin release persisted, to a limited extent, in islets exposed to 20 mM K+, but was abolished in islets exposed to 50 mM K+. At the latter concentration, however, K+ was still able to augment 45Ca outflow and insulin secretion from islets first exposed to gliclazide. These findings support the view that the depolarization of the B-cell membrane plays a critical role in the stimulus-secretion coupling of sulfonylurea-induced insulin release.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations; D004305:Dose-Response Relationship, Drug; D005907:Gliclazide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013997:Time Factors
D002412:Cations; D007328:Insulin; D007473:Ion Channels; D013453:Sulfonylurea Compounds; D005907:Gliclazide; D011188:Potassium; D002118:Calcium